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Sökning: WFRF:(Rukh Gull)

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1.
  • Affatato, Oreste, et al. (författare)
  • Assessing volumetric brain differences in migraine and depression patients : a UK Biobank study
  • 2023
  • Ingår i: BMC Neurology. - : BMC. - 1471-2377. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Migraine and depression are two of the most common and debilitating conditions. From a clinical perspective, they are mostly prevalent in women and manifest a partial overlapping symptomatology. Despite the high level of comorbidity, previous studies hardly investigated possible common patterns in brain volumetric differences compared to healthy subjects. Therefore, the current study investigates and compares the volumetric difference patterns in sub-cortical regions between participants with migraine or depression in comparison to healthy controls.Methods: The study included data from 43 930 participants of the large UK Biobank cohort. Using official ICD10 diagnosis, we selected 712 participants with migraine, 1 853 with depression and 23 942 healthy controls. We estimated mean volumetric difference between the groups for the different sub-cortical brain regions using generalized linear regression models, conditioning the model within the levels of BMI, age, sex, ethnical background, diastolic blood pressure, current tobacco smoking, alcohol intake frequency, Assessment Centre, Indices of Multiple Deprivation, comorbidities and total brain volume.Results: We detected larger overall volume of the caudate (mean difference: 66, 95% CI [-3, 135]) and of the thalamus (mean difference: 103 mm(3), 95% CI [-2, 208]) in migraineurs than healthy controls. We also observed that individuals with depression appear to have also larger overall (mean difference: 47 mm(3), 95% CI [-7, 100]) and gray matter (mean difference: 49 mm(3), 95% CI [2, 95]) putamen volumes than healthy controls, as well as larger amygdala volume (mean difference: 17 mm(3), 95% CI [-7, 40]).Conclusion: Migraineurs manifested larger overall volumes at the level of the nucleus caudate and of the thalamus, which might imply abnormal pain modulation and increased migraine susceptibility. Larger amygdala and putamen volumes in participants with depression than controls might be due to increased neuronal activity in these regions.
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2.
  • Affatato, Oreste, et al. (författare)
  • Volumetric Differences in Cerebellum and Brainstem in Patients with Migraine : A UK Biobank Study
  • 2023
  • Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 11:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The cerebellum and the brainstem are two brain structures involved in pain processing and modulation that have also been associated with migraine pathophysiology. The aim of this study was to investigate possible associations between the morphology of the cerebellum and brainstem and migraine, focusing on gray matter differences in these brain areas.Methods: The analyses were based on data from 712 individuals with migraine and 45,681 healthy controls from the UK Biobank study. Generalized linear models were used to estimate the mean gray matter volumetric differences in the brainstem and the cerebellum. The models were adjusted for important biological covariates such as BMI, age, sex, total brain volume, diastolic blood pressure, alcohol intake frequency, current tobacco smoking, assessment center, material deprivation, ethnic background, and a wide variety of health conditions. Secondary analyses investigated volumetric correlation between cerebellar sub-regions.Results: We found larger gray matter volumes in the cerebellar sub-regions V (mean difference: 72 mm3, 95% CI [13, 132]), crus I (mean difference: 259 mm3, 95% CI [9, 510]), VIIIa (mean difference: 120 mm3, 95% CI [0.9, 238]), and X (mean difference: 14 mm3, 95% CI [1, 27]).Conclusions: Individuals with migraine show larger gray matter volumes in several cerebellar sub-regions than controls. These findings support the hypothesis that the cerebellum plays a role in the pathophysiology of migraine.
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3.
  • Ahmad, Shafqat, et al. (författare)
  • Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry
  • 2013
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:7, s. 1003607-1003607
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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4.
  • Ahmad, Shafqat, et al. (författare)
  • Gene Lifestyle Interactions With Relation to Obesity, Cardiometabolic, and Cardiovascular Traits Among South Asians
  • 2019
  • Ingår i: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 10
  • Forskningsöversikt (refereegranskat)abstract
    • The rapid rise of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) during the last few decades among South Asians has been largely attributed to a major shift in lifestyles including physical inactivity, unhealthy dietary patterns, and an overall pattern of sedentary lifestyle. Genetic predisposition to these cardiometabolic risk factors may have interacted with these obesogenic environments in determining the higher cardiometabolic disease prevalence. Based on the premise that gene-environment interactions cause obesity and cardiometabolic diseases, we systematically searched the literature and considered the knowledge gaps that future studies might ful fill. We identified only seven published studies that focused specifically on gene-environment interactions for cardiometabolic traits in South Asians, most of which were limited by relatively small sample and lack of replication. Some studies reported that the differences in metabolic response to higher physical activity and low caloric diet might be modified by genetic risk related to these cardiometabolic traits. Although studies on gene lifestyle interactions in cardiometabolic traits report significant interactions, future studies must focus on more precise assessment of lifestyle factors, investigation of a larger set of genetic variants and the application of powerful statistical methods to facilitate translatable approaches. Future studies should also be integrated with findings both using mechanistic studies through laboratory settings and randomized clinical trials for clinical outcomes.
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5.
  • Ahmad, Shafqat, et al. (författare)
  • Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry
  • 2013
  • Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607-
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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6.
  • Alsehli, Ahmed M., et al. (författare)
  • Differential associations of statin treatment and polymorphism in genes coding for HMGCR and PCSK9 to risk for insomnia
  • 2021
  • Ingår i: Frontiers in Bioscience-Landmark. - : Frontiers Media S.A.. - 2768-6701 .- 2768-6698. ; 26:12, s. 1453-1463
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Statins have been linked to an increased risk for insomnia, but the literature is controversial. Moreover, it is unknown, if the potential effects are directly related to the inhibition of the statin target HMGCR, the subsequently lowered cholesterol levels, or other off-target effects of statins. Aims: To investigate the association of statin treatment and genetic proxies of cholesterol lowering drugs with the risk for insomnia and chronotype in a large population-based cohort. Methods: A cross-sectional cohort study based on baseline data collected between 2006–2010 in UK biobank cohort was conducted. European participants without any history of psychiatric/neurological disorders or of stroke and with available genetic data as well as information on statin use were included in the present study. Self-reported measures of insomnia and chronotype were analysed (a) in statin users versus control subjects, (b) subjects carrying single nucleotide polymorphisms (SNPs) in the HMGCR gene, which are associated with reduced enzymatic function and lower cholesterol levels (rs17238484 and rs12916) and (c) subjects carrying a SNP in the PCSK9 gene (rs1159147), which leads to lower cholesterol levels independent of HMGCR. The main analysis were performed using multivariable regression models. Statin treatment and SNPs in HMGCR and PCSK9 genes were used as exposures and main outcomes were insomnia and chronotype. Results: A total of 206,801participants (mean [SD] age, 57.5 [7.9] years; 56% women; 20% statin users) were included in the present study. Statin users had an increased risk of insomnia compared to controls (odds ratio [95% CI], 1.07 [1.03 to 1.11]; p = 1.42 × 10−4). A similar effect was observed for PCSK9 rs11591147-T allele (1.07 [1.01–1.14]; 0.014), while the two gene variants of HMGCR were associated with a reduced risk for insomnia (rs17238484-G: 0.97 [0.95 to 0.99]; 0.014 and rs12916-T: 0.97 [0.96 to 0.99]; 0.002). In regard to chronotype, there was no effect of either statin treatment or HMGCR SNPs, but the PCSK9 rs11591147-T allele was associated with a higher evening preference (1.17 [1.06 to 1.29]; 0.001). Conclusion: Our data suggests that statin treatment can pose an increased risk for insomnia in in the European population. Interestingly, there was no agreement between the effects of statins and the effects of reduced HMGCR activity based on genetic variants, suggesting that the observed unfavourable effect of statins on sleep is conveyed through other targets. This further explains why the literature on statin effects on sleep is not conclusive. Finally our data encourage further investigations into the molecular processes linking statins, HMGCR and PCSK9 to sleep behaviour.
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7.
  • Berkins, Samuel, et al. (författare)
  • Depression and Vegetarians : Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes
  • 2021
  • Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.
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8.
  • Brunkwall, Louise, et al. (författare)
  • Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts
  • 2016
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 104:3, s. 809-815
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The consumption of sugar-sweetened beverages (SSBs), which has increased substantially during the last decades, has been associated with obesity and weight gain.Objective: Common genetic susceptibility to obesity has been shown to modify the association between SSB intake and obesity risk in 3 prospective cohorts from the United States. We aimed to replicate these findings in 2 large Swedish cohorts.Design: Data were available for 21,824 healthy participants from the Malmö Diet and Cancer study and 4902 healthy participants from the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk Study. Self-reported SSB intake was categorized into 4 levels (seldom, low, medium, and high). Unweighted and weighted genetic risk scores (GRSs) were constructed based on 30 body mass index [(BMI) in kg/m2]-associated loci, and effect modification was assessed in linear regression equations by modeling the product and marginal effects of the GRS and SSB intake adjusted for age-, sex-, and cohort-specific covariates, with BMI as the outcome. In a secondary analysis, models were additionally adjusted for putative confounders (total energy intake, alcohol consumption, smoking status, and physical activity).Results: In an inverse variance-weighted fixed-effects meta-analysis, each SSB intake category increment was associated with a 0.18 higher BMI (SE = 0.02; P = 1.7 × 10−20; n = 26,726). In the fully adjusted model, a nominal significant interaction between SSB intake category and the unweighted GRS was observed (P-interaction = 0.03). Comparing the participants within the top and bottom quartiles of the GRS to each increment in SSB intake was associated with 0.24 (SE = 0.04; P = 2.9 × 10−8; n = 6766) and 0.15 (SE = 0.04; P = 1.3 × 10−4; n = 6835) higher BMIs, respectively.Conclusions: The interaction observed in the Swedish cohorts is similar in magnitude to the previous analysis in US cohorts and indicates that the relation of SSB intake and BMI is stronger in people genetically predisposed to obesity.
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9.
  • Dahlén, Amelia, et al. (författare)
  • The influence of personality on the risk of myocardial infarction in UK Biobank cohort
  • 2022
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Personality is a strong determinant for several health-related behaviours and has been linked to the development of cardiovascular diseases. However, the reports of personality's mediating role have been inconsistent with no data available from large population-based cohorts. The study aimed to create proxies for the Big Five personality traits, extraversion, agreeableness, conscientiousness, openness and neuroticism, to examine the longitudinal relationship between personality and myocardial infarction in the UK Biobank. The study sample comprised of 484,205 participants (55% female, 45% male, mean age 56.4 +/- 8.1 years) from UK Biobank cohort with a mean follow-up of 7 years. The personality proxies sociability, warmth, diligence, curiosity and nervousness were created using self-reported data on psychological factors, mental health and social support, to match the facets of the Big Five traits. As neuroticism is the only Big Five personality trait available in the UK Biobank, it was included to validate the personality proxies. Myocardial infarction outcome information was collected from hospital records, death registries or was self-reported. Logistic regression and Cox proportional hazard regression were used to estimate odds ratio (OR) and hazard ratios (HR), respectively with 95% confidence intervals (CI) adjusted for demographics (age, sex, socioeconomic status, ethnicity), health-related factors (BMI, diabetes, systolic and diastolic blood pressure) and lifestyle factors (alcohol intake, smoking, and moderate-to-vigorous physical activity). Diligence was found to be significantly associated with lower prevalent myocardial infarction [OR: 0.87; (CI 0.84-0.89)] and lower incident myocardial infarction [HR: 0.88; (CI 0.85-0.92)]. Sociability was also protective against prevalent [OR: 0.89; (CI 0.87-0.92)] and incident [HR: 0.90; (CI 0.87-0.93)] myocardial infarction. Conversely, nervousness inferred a higher risk for both prevalent [OR: 1.10; (CI 1.08-1.12)] and incident [HR: 1.07; (CI 1.04-1.09)] myocardial infarction during follow-up. Sex-stratified analyses revealed that nervousness significantly increases the risk for incident myocardial infarction among women [HR: 1.13; (CI 1.08-1.19)] compared to men [HR: 1.05; (CI 1.02-1.08)]. By using our created proxies, we were able to investigate the impact of personality on the development of myocardial infarction. Persons with higher levels of diligence and sociability mimicking predominantly conscientiousness and extraversion personalities respectively are less likely to experience myocardial infarction, while personalities predominantly characterised by nervousness pose higher risk for developing myocardial infarction. These initial findings invite further validation of the use of the personality proxies in UK Biobank cohort.
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10.
  • Dartora, Caroline, et al. (författare)
  • A deep learning model for brain age prediction using minimally preprocessed T1w images as input
  • 2023
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: In the last few years, several models trying to calculate the biological brain age have been proposed based on structural magnetic resonance imaging scans (T1-weighted MRIs, T1w) using multivariate methods and machine learning. We developed and validated a convolutional neural network (CNN)-based biological brain age prediction model that uses one T1w MRI preprocessing step when applying the model to external datasets to simplify implementation and increase accessibility in research settings. Our model only requires rigid image registration to the MNI space, which is an advantage compared to previous methods that require more preprocessing steps, such as feature extraction. Methods: We used a multicohort dataset of cognitively healthy individuals (age range = 32.0–95.7 years) comprising 17,296 MRIs for training and evaluation. We compared our model using hold-out (CNN1) and cross-validation (CNN2–4) approaches. To verify generalisability, we used two external datasets with different populations and MRI scan characteristics to evaluate the model. To demonstrate its usability, we included the external dataset’s images in the cross-validation training (CNN3). To ensure that our model used only the brain signal on the image, we also predicted brain age using skull-stripped images (CNN4). Results: The trained models achieved a mean absolute error of 2.99, 2.67, 2.67, and 3.08 years for CNN1–4, respectively. The model’s performance in the external dataset was in the typical range of mean absolute error (MAE) found in the literature for testing sets. Adding the external dataset to the training set (CNN3), overall, MAE is unaffected, but individual cohort MAE improves (5.63–2.25 years). Salience maps of predictions reveal that periventricular, temporal, and insular regions are the most important for age prediction. Discussion: We provide indicators for using biological (predicted) brain age as a metric for age correction in neuroimaging studies as an alternative to the traditional chronological age. In conclusion, using different approaches, our CNN-based model showed good performance using one T1w brain MRI preprocessing step. The proposed CNN model is made publicly available for the research community to be easily implemented and used to study ageing and age-related disorders.
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11.
  • de Jorge Martínez, Clara, et al. (författare)
  • Genetics of anorexia nervosa : An overview of genome-wide association studies and emerging biological links
  • 2022
  • Ingår i: Journal of genetics and genomics = Yi chuan xue bao. - : Elsevier. - 1673-8527. ; 49:1, s. 1-12
  • Forskningsöversikt (refereegranskat)abstract
    • Anorexia nervosa (AN) is a complex disorder with a strong genetic component. Comorbidities are frequent and there is substantial overlap with other disorders. The lack of understanding of the molecular and neuroanatomical causes has made it difficult to develop effective treatments and it is often difficult to treat in clinical practice. Recent advances in genetics have changed our understanding of polygenic diseases, increasing the possibility of understanding better how molecular pathways are intertwined. This review synthetizes the current state of genetic research providing an overview of genome-wide association studies (GWAS) findings in AN as well as overlap with other disorders, traits, pathways, and imaging results. This paper also discusses the different putative global pathways that are contributing to the disease including the evidence for metabolic and psychiatric origin of the disease.
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12.
  • de Ruijter, Markus J. T., et al. (författare)
  • Association of Diligence and Sociability with Stroke : A UK Biobank Study on Personality Proxies
  • 2022
  • Ingår i: FRONTIERS IN BIOSCIENCE-LANDMARK. - : IMR Press. - 2768-6701 .- 2768-6698. ; 27:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a growing interest in how personality may be related to the risk of developing disease. Associations between personality and stroke have so far only been studied in relation to stroke mortality. However, many stroke survivors suffer severe impairment of quality of life due to sequelae such as aphasia, hemiparesis, depression and anxiety. In this study we assess the association between personality and risk of stroke, regardless of mortality. Methods: Using self-reported data on psychological factors, mental health and social support, proxies for the Big Five personality traits were developed for 482,535 participants in the UK Biobank. Logistic regression and Cox proportional hazard models, with 95% confidence intervals (CI), were used to estimate odds ratios (OR) and hazard ratios (HR) between each personality trait and stroke prevalence (N = 6793) and incidence (N = 3312), respectively. Models were adjusted for demographic, health-related, and lifestyle factors. Results: Diligence and sociability were associated with a lower risk of stroke incidence in the fully adjusted model (respectively: [HR = 0.92; 95% CI = (0.88, 0.96)], [HR = 0.93; 95% CI = (0.89, 0.97)]). However, nervousness, curiosity and warmth were not significantly associated with a risk of stroke incidence. Conclusions: Individuals with higher levels of diligence and sociability may be at a reduced risk of developing stroke. With respect to the debated role of neuroticism in relation to cardiovascular disease, we did not find evidence of an association between nervousness and risk of developing stroke.
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13.
  • de Ruijter, Markus J. T., et al. (författare)
  • Job satisfaction has differential associations with delay discounting and risk-taking
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Low job satisfaction has been associated with both negative health and negative organizational outcomes. Knowledge on which factors influence job satisfaction remains limited. This study assesses the associations between job satisfaction and three personality traits related to cognitive- and inhibitory control: delay discounting, risk-taking and sensation seeking (DRS-traits). Delay discounting and sensation seeking were inferred using self-reported behavioral data and health measurements for 80,676 participants in the UK Biobank. Multiple linear regression analysis produced beta coefficients and confidence intervals for each DRS-trait and job satisfaction. Analyses were adjusted for age, socioeconomic status and sleep quality. A combination of the three DRS-traits (CDRS) was assessed as well. Delay discounting and risk-taking were associated with, respectively, lower and higher job satisfaction in both sexes. Sensation seeking had no significant association with job satisfaction for either sex. The combined score, CDRS, was only negatively associated with job satisfaction in females but not in males. We discuss that the negative association between delay discounting and job satisfaction may be due to career related delay discounting effects, but also highlight that low job satisfaction itself may also lead to increased delay discounting. Additionally, we discuss why increased risk-taking behavior may have a positive effect on job satisfaction.
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14.
  • de Ruijter, Markus J. T. (författare)
  • Mind & Well-being : The relationships between personality and health related pathology
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The study of the associations between personality, lifestyle and health related pathology has revealed important associations. These include associations with physical health such as the onset of cardiovascular disease, but also with mental and emotional health such as depression or life satisfaction. However, certain gaps in knowledge and methodology had persisted. This thesis contains several works that address those gaps and extend the knowledge and methodology in personality-related research.Study I utilized the large-scale UK Biobank cohort to examine personality traits in association with stroke risk. Proxy variables for the Big Five personality traits were inferred from the available data. Results indicate negative associations of the personality traits diligence and sociability, with incident stroke risk, suggesting potential protective effects.Study II employed Mendelian randomization to investigate causal relationships between specific subcategories of neuroticism and different subtypes of cardiovascular disease. Using the UK Biobank cohort, the study showed causal positive associations between depressed affect and two subtypes of cardiovascular disease: heart failure and myocardial infarction.Study III examined the associations between job satisfaction and personality traits related to executive functions: delay discounting, risk-taking, and sensation seeking. Proxy variables were created to infer delay-discounting and sensation seeking. Using data available in the UK Biobank, the study reveals a negative association between delay discounting and job satisfaction, and a positive association between risk-taking and job satisfaction.Study IV explored the association between genetic risk for autism spectrum disorder (ASD) and well-being in the general public, regardless of ASD diagnosis. The study employs polygenic risk scoring in the UK Biobank cohort and shows that the genetic risk for ASD is associated with all five well-being spectrum traits in a detrimental way, emphasizing the potential impact of a genetic predisposition for ASD on well-being.Finally, in Study V, the research proposed a novel method for studying general personality in Drosophila melanogaster. The method includes a new experimental environment, comprehensive recording and tracking, and subsequent analysis techniques, providing a foundation for further research into personality-like traits in the species.Overall, this thesis extends the knowledge and methodology in personality-related research and highlights the potential impact of personality traits on physical and mental well-being.
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15.
  • Ericson, Ulrika, et al. (författare)
  • Sex-specific interactions between the IRS1 polymorphism and intakes of carbohydrates and fat on incident type 2 diabetes.
  • 2012
  • Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The minor T allele of rs2943641 near the gene encoding for insulin receptor substrate 1 (IRS1) has been associated with decreased risk of type 2 diabetes (T2D) and adiposity in genome-wide association studies. Dietary intake can influence the regulation of IRS1, and studies have indicated sex-specific associations between IRS1 and adiposity. OBJECTIVE: The objective was to examine the interaction between IRS1 rs2943641 and macronutrient intakes on incident T2D and percentage body fat in the Malmö Diet and Cancer cohort. DESIGN: The study included 15,227 women and 9614 men aged 45-74 y without prevalent diabetes. Dietary data were collected with a modified diet history method. During 12 y follow-up, 1567 incident T2D cases were identified. RESULTS: The T allele was associated with lower incidence of T2D (P-trend = 0.003) and, in men, with higher percentage body fat (P-trend = 0.00002). We observed 3-way interactions between sex, rs2943641, and carbohydrate intake (P = 0.01) as well as between sex, rs2943641, and fat intake (P = 0.01) on incident T2D. Among women, the T allele was associated with decreased risk only in the lower tertiles of carbohydrate intake (P-trend = 0.01, P-interaction = 0.01). In contrast, among men, the T allele was associated with decreased risk in the lowest tertile of fat intake (P-trend = 0.01, P-interaction = 0.02). No interaction was observed between macronutrient intakes and rs2943641 on percentage body fat. CONCLUSIONS: Our results indicate that IRS1 rs2943641 interacts with carbohydrate and fat intakes on incident T2D in a sex-specific fashion. A protective association between the rs2943641 T allele and T2D was restricted to women with low carbohydrate intake and to men with low fat intake.
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16.
  • Gaudio, Santino, et al. (författare)
  • Higher fresh fruit intake relates to larger grey matter volumes in areas involved in dementia and depression : A UK Biobank study
  • 2023
  • Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 283
  • Tidskriftsartikel (refereegranskat)abstract
    • The benefits of consuming fruits and vegetables are widely accepted. While previous studies suggest a protective role of fruits and vegetables against a variety of diseases such as dementia and depression, the biological mechanisms/effects remain unclear. Here we investigated the effect of fruit and vegetable consumption on brain structure. Particularly on grey matter (GM) and white matter (WM) volumes, regional GM volumes and subcortical volumes. Cross-sectional imaging data from UK Biobank cohort was used. A total of 9925 participants (Mean age 62.4 +/- 7.5 years, 51.1 % men) were included in the present analysis. Measures included fruit and vegetable intake, other dietary patterns and a number of selected lifestyle factors and clinical data. Brain volumes were derived from structural brain magnetic resonance imaging. General linear model was used to study the associations between brain volumes and fruit/vegetable intakes. After adjusting for selected confounding factors, salad/raw vegetable intake showed a positive association with total white matter volume, fresh fruit intake showed a negative association with total grey matter (GM) volume. Regional GM analyses showed that higher fresh fruit intake was associated with larger GM volume in the left hippocampus, right temporal occipital fusiform cortex, left postcentral gyrus, right precentral gyrus, and right juxtapositional lobule cortex. We conclude that fruit and vegetable consumption seems to specifically modulate brain volumes. In particular, fresh fruit intake may have a protective role in specific cortical areas such as the hippocampus, areas robustly involved in the pathophysiology of dementia and depression.
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18.
  • Gentreau, Mélissa, et al. (författare)
  • The effects of statins on cognitive performance are mediated by low-density lipoprotein, C-reactive protein and blood glucose concentrations.
  • 2023
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Statins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, C-Reactive Protein (CRP), and vitamin D biomarkers mediated this association. We used participants from the UK biobank aged 40 to 69 without neurological and psychiatric disorders (n = 147,502 and n = 24,355, respectively). We performed linear regression to evaluate the association between statin use and cognitive performance and, mediation analysis to quantify the total, direct, indirect effects and the proportion meditated by blood biomarkers. Statin use was associated with lower cognitive performance at baseline (β = -0.40 [-0.53, -0.28], P = <.0001) and this association was mediated by LDL (Proportion mediated = 51.4%, P = 0.002), CRP (Proportion mediated = -11%, P = 0.006) and blood glucose (Proportion mediated = 2.6%, P = 0.018) concentrations. However, statin use was not associated with cognitive performance, measured 8 years later (β = -0.003 [-0.11, 0.10], P = 0.96). Our findings suggest that statins are associated with lower short-term cognitive performance by lowering LDL and raising blood glucose concentrations, and better performance by lowering CRP concentrations. In contrast, statins have no effect on long-term cognition and remain beneficial in reducing cardiovascular risk factors.
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19.
  • Hertel, Jens K., et al. (författare)
  • FTO, Type 2 Diabetes, and Weight Gain Throughout Adult Life A Meta-Analysis of 41,504 Subjects From the Scandinavian HUNT, MDC, and MPP Studies
  • 2011
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 60:5, s. 1637-1644
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO) influences BMI across adult life span. RESEARCH DESIGN AND METHODS-Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmo Diet and Cancer (MDC) and Malmo Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians. RESULTS-The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 x 10(-8)) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 x 10(-8)). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m(2) per risk allele; P = 2.0 x 10(-26), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (Delta BMI = 0.0 [-0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS-We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter. Diabetes 60:1637-1644, 2011
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20.
  • Hindy, George, et al. (författare)
  • Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes
  • 2016
  • Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: TCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence. Results: We included 26,905 individuals without diabetes from the Malmö Diet and Cancer Study cohort. Diet data was collected at baseline using a food frequency questionnaire, a 7-day food record, and an interview. Altogether, 51 gene loci were analyzed for putative links to WNT signaling. Over a mean follow-up period of 14.7 years, 3132 incident cases of type 2 diabetes were recorded. Seven genes (nine single nucleotide polymorphisms (SNPs)) were annotated as involved in WNT signaling including TCF7L2 (rs7903146 and rs12255372), HHEX (rs1111875), HNF1A (rs7957197), NOTCH2 (rs10923931), TLE4 (rs13292136), ZBED3 (rs4457053), and PPARG (rs1801282 and rs13081389). SNPs in TCF7L2, NOTCH2, and ZBED3 showed significant interactions with fiber intake on type 2 diabetes incidence (Pinteraction = 0.034, 0.005, 0.017, and 0.002, respectively). The magnitude of the association between the TCF7L2 risk allele and incident type 2 diabetes increased from the lowest to the highest quintiles of fiber intake. Higher fiber associated with lower type 2 diabetes risk only among risk allele carriers of the NOTCH2 variant and homozygotes of the risk allele of the ZBED3 variant. Conclusions: Our results suggest that several type 2 diabetes susceptibility SNPs in genes involved in WNT signaling may interact with dietary fiber intake on type 2 diabetes incidence.
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21.
  • Lafta, Muataz S., et al. (författare)
  • Exploring sex differences : insights into gene expression, neuroanatomy, neurochemistry, cognition, and pathology
  • 2024
  • Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 18
  • Forskningsöversikt (refereegranskat)abstract
    • Increased knowledge about sex differences is important for development of individualized treatments against many diseases as well as understanding behavioral and pathological differences. This review summarizes sex chromosome effects on gene expression, epigenetics, and hormones in relation to the brain. We explore neuroanatomy, neurochemistry, cognition, and brain pathology aiming to explain the current state of the art. While some domains exhibit strong differences, others reveal subtle differences whose overall significance warrants clarification. We hope that the current review increases awareness and serves as a basis for the planning of future studies that consider both sexes equally regarding similarities and differences.
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22.
  • Miguet, Maud, et al. (författare)
  • Important Difference between Occupational Hazard Exposure among Shift Workers and Other Workers; Comparing Workplace before and after 1980
  • 2020
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:20
  • Tidskriftsartikel (refereegranskat)abstract
    • Improving health and safety at work has been an important issue for the European Union since the 1980s. The existing literature supports that shift work is associated with multiple indicators of poor health but frequently neglects the potential impact of occupational hazards. This study aims at describing and comparing the exposure to different workplace hazards among shift and other workers before and after 1980. Exposure to different workplace hazards (noise, dust, pollutant, and other physical stressors) were analyzed among 119,413 participants from the UK Biobank cohort. After stratifying the analyses before and after 1980, exposure was compared between shift and other workers. Potential confounding variables (sex, age, ethnicity, education level, occupational category, and neuroticism) were adjusted for in the log-binomial regression. Shift workers had a higher prevalence ratio (PR) than other workers of being exposed to almost all identified hazards both before or after 1980. They were also more likely to be exposed to multiple hazards compared to other workers, both before 1980 (PR: 1.25; 95% CI: 1.21-1.30) and after 1980 (PR: 1.34; 95% CI: 1.30-1.38). The prevalence of all measured risk factors was higher after 1980 than before 1980 among shift workers. Of note, the work environment has improved overall for other workers. Our findings suggest that changes at the workplace have benefited other workers more than shift workers as they are still more exposed to all occupational hazards.
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23.
  • Miguet, Maud, et al. (författare)
  • Time spent outdoors and risk of myocardial infarction and stroke in middle and old aged adults : Results from the UK Biobank prospective cohort
  • 2021
  • Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 199
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTime spent outdoors has been previously related to several cardiovascular risk factors, implying that it may confer either beneficial or harmful effects on cardiovascular health. However, no large population-based studies have examined the relation between time spent outdoors and myocardial infarction and stroke.ObjectivesWe aimed to investigate the longitudinal relation between time spent outdoors and myocardial infarction and stroke in large UK population‐based cohort.MethodsA total of 446,648 participants from UK Biobank were included in the study of which 431,146 participants (56% females and 44% males with a mean age of 56.4 ± 8.1 years) were followed for a median time of 7 years. Time spent outdoors was self-reported and participants were stratified into quantiles (less than 1.5 [reference group]; 1.5 to 2.4; 2.5 to 3.5 and more than 3.5 h per day outdoors). Myocardial infarction and stroke events were either collected from hospital records and death registries or were self-reported by the participants. Cox proportional hazard regression was used for the analysis. In addition to age and sex, analyses were adjusted for potential demographic (TDI, ethnic background, current employment status), lifestyle (alcohol intake frequency, current tobacco use, sedentary time and moderate-to-vigorous physical activity), health related factors (BMI, systolic and diastolic blood pressure) and environmental indicators (NO2, NOx, PM10, PM2.5-10, PM2,5, noise pollution, % greenspace, % natural environment and % water).ResultsA 20% increased risk for myocardial infarction incidence was observed among participants who reported spending more than 3.5 h/day outdoors (HR: 1.20, 95% CI: 1.06–1.36) compared to the reference group. A trend was also observed for stroke (HR: 1.14, 95% CI: 0.97–1.34).ConclusionFindings from the present study indicate that spending more than 3.5 h/day outdoors is a risk factor for myocardial infarction and stroke. Future research is needed to further understand the relation between time spent outdoors and cardiovascular disease.
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24.
  • Mohamed, Mohamed S., et al. (författare)
  • Differential change in alcohol consumption during the COVID-19 pandemic : the role of loneliness, socialization, and mental well-being
  • 2024
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The COVID-19 pandemic led to a surge in mental health issues and psychological distress, disruption to work/studying conditions, and social isolation particularly among young adults. Changes in these factors are differentially associated with alcohol use. Moreover, the relationship between these factors are bidirectional and may have fluctuated throughout the different phases of the pandemic. However, studies focusing on young adults had conflicting results, short follow-up periods, and lacked comprehensive data to describe underlying mechanisms.Methods: 1067 young adults participated in repetitive measures termed wave 4 (2021) of the Survey of Adolescent Life in Västmanland Cohort “SALVe” Cohort. Of these, 889 also completed pre-pandemic measurements termed wave 3 (2018). Participants completed the Alcohol Use Disorders Identification Test (AUDIT) to evaluate alcohol consumption and harmful use. Cross-sectional associations between perceived changes in alcohol use and shift in individual, mental health, and work environment factors were examined using Chi-square tests. Logistic regression was utilized to identify pre-pandemic predictors of harmful consumption during the pandemic.Results: Harmful consumption decreased only in females following the COVID-19 pandemic. Participants who reported increased feelings of depression, anxiety, and loneliness were more likely to increase their alcohol use. Interestingly, the subgroup who felt less lonely and met their friends more often, as well as those who continued working/studying from their regular workplace also had an increased likelihood of higher consumption. Only pre-pandemic ADHD and delinquency symptoms predicted harmful alcohol consumption following the pandemic.Conclusion: Females reduced harmful alcohol consumption during the COVID-19 pandemic. While those who suffered the burden of social isolation and distress were more likely to increase their alcohol use, young adults who felt less lonely and met their friends more often also had a similar outcome. The relationship between loneliness and alcohol consumption among young adults is influenced by the social factors that may be facilitated by drinking.
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25.
  • Mohamed, Mohamed S., et al. (författare)
  • Worsened Anxiety and Loneliness Influenced Gaming and Gambling during the COVID-19 Pandemic
  • 2023
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To study the prevalence and patterns of problematic gaming and gambling during the COVID-19 pandemic and the association with psychiatric traits and major types of anxiety categories.Method: 1067 young adults participated in both wave 3 (2018) and wave 4 (2021) of the SALVe Cohort. Associations with psychiatric symptoms and anxiety were examined using logistic regression and Chi-square tests.Results: Problematic gaming decreased by 1.3 percentage points to 23.2% since the start of the pandemic, while problematic gambling increased by 0.9 percentage points to 6.5% in w4. Average time spent playing video games/day decreased from 2.2 h (w3) to 1.7 h (w4), while increases in gaming activity were associated with worsened feelings of loneliness (p = 0.002), depression (p < 0.001), and anxiety (p < 0.01) during the pandemic. Predictors for problematic gaming at w4 were previous problematic gaming and social anxiety (p = < 0.001 and 0.01, respectively). Moreover, previous problem gambling also predicted problem gambling at w4 p < 0.001. All anxiety categories were associated with both problematic gaming and gambling when adjusted for age and sex. However, after adjusting for depression and insomnia, social anxiety was associated with problematic gaming (p < 0.001), while panic was associated with problem gambling (p < 0.001).Conclusion: Overall, problematic gaming has decreased since the start of the pandemic, while problem gambling has increased. Worsened feelings of loneliness, depression, and anxiety during the pandemic are associated with increased gaming. Moreover, the association between problematic gaming and gambling and anxiety is independent of depression and sleep problems.
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26.
  • Mohammad, Salahuddin, et al. (författare)
  • Job satisfaction and job tenure of people with mental health disorders : a UK Biobank cohort study
  • 2023
  • Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 51:8, s. 1248-1257
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims:Job satisfaction plays an important role for the life quality and health of working individuals. While studies have shown that self-reported mental health conditions such as stress, anxiety and depression are associated with job satisfaction, a large population-based study exploring and comparing self-reported physician posed diagnosed conditions and their association with job satisfaction and job tenure is missing. This study addresses the gap along with exploring the impact of the neurotic personality trait and other possible contributing factors.Methods:Sixteen mental health disorders diagnosed by physicians, categorised into four major groups were investigated in relation to employment status (108,711 participants) and in relation to job satisfaction and job tenure (34,808 participants). Analyses were performed using linear regression adjusted for age, sex, townsend deprivation index, body mass index, education, physical activity, work hours and neuroticism.Results:Neurotic and stress disorders, eating disorders and other mental health disorders were strongly associated with lower job satisfaction and shorter job tenure in both unadjusted and adjusted analyses. Neuroticism was strongly linked to job satisfaction but was not associated with job tenure.Conclusions:Study findings clarify the complex relationship of mental health with job satisfaction and job tenure, which is very important to understand in designing measures to improve working life participation of individuals with mental health issues.
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27.
  • Mohammad, Salahuddin, et al. (författare)
  • Well-being spectrum traits are associated with polygenic scores for autism
  • 2023
  • Ingår i: Autism Research. - : John Wiley & Sons. - 1939-3792 .- 1939-3806. ; 16:10, s. 1891-1902
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals with autism spectrum disorder (ASD) tend to experience lower well-being as demonstrated mostly for children and adolescents in epidemiological studies. A further investigation of inclusive well-being, in terms of five well-being spectrum (5-WBS) traits including neuroticism, depression, loneliness, life satisfaction, and positive affect, among adults with ASD may deepen our understanding of their well-being, and lead to the possibility to further modify societal supportive mechanisms for individuals with ASD. This study aims to investigate if a genetic predisposition for ASD is associated with 5-WBS traits using polygenic risk score (PRS) analysis. PRS for ASD were calculated based on the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and were created in the independent cohort UK Biobank. Regression analyses were performed to investigate the association between ASD PRS and 5-WBS traits in the UK Biobank population including 337,423 individuals. ASD PRS were significantly associated with all 5-WBS traits, showing a positive association with the negative WBS traits, neuroticism (max R2 = 0.04%, p < 1 × 10−4), depression (max R2 = 0.06%, p < 1 × 10−4), loneliness (max R2 = 0.04%, p < 1 × 10−4), and a negative association with the positive WBS traits, life satisfaction (max R2 = 0.08%, p < 1 × 10−4), positive affect (max R2 = 0.10%, p < 1 × 10−4). The findings suggest that adults carrying a high load of risk single nucleotide peptides (SNPs) for ASD are more likely to report decreased well-being. The study demonstrates a considerable connection between susceptibility to ASD, its underlying genetic etiology and well-being.
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28.
  • Nettleton, Jennifer A, et al. (författare)
  • Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry
  • 2015
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 24:16, s. 4728-4738
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
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29.
  • Norby, Faye L, et al. (författare)
  • Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation : The AFGen Consortium
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts.METHODS: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score.RESULTS: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04).CONCLUSIONS: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
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30.
  • Pisanu, Claudia, et al. (författare)
  • Association between migraine prevalence, treatment with proton-pump inhibitors and CYP2C19 phenotypes in UK Biobank
  • 2021
  • Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier. - 0753-3322 .- 1950-6007. ; 143
  • Tidskriftsartikel (refereegranskat)abstract
    • Proton-pump inhibitors (PPIs) are used to suppress gastric acid secretion in several gastrointestinal conditions. While these drugs are generally well tolerated, their long-term use may be associated with different adverse effects, including migraine. We analyzed the association between treatment with PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole) and migraine prevalence in the UK Biobank cohort through a cross-sectional analysis (using baseline data for 468,280 participants, 16,390 of whom had migraine) and a longitudinal analysis (including 145,007 participants with no migraine at baseline, of whom 3786 had probable migraine without aura [MWOA] and 9981 probable migraine with aura [MWA] or both MWOA and MWA at an average follow-up time of 10.06 years). We also evaluated the modulating role of the metabolizer phenotype of CYP2C19, the major enzyme involved in PPI clearance. Treatment with PPIs was associated with higher migraine prevalence at baseline (odds ratio [OR] = 1.25, p < 0.0001). CYP2C19 rapid metabolizer phenotype was associated with lower prevalence of migraine exclusively in participants treated with PPIs (OR = 0.89, p = 0.029). In addition, treatment with PPIs was associated with higher incidence of both probable MWOA (OR = 1.24, p = 0.002) and MWA (OR = 1.43, p < 0.0001) at follow-up. Treatment with PPIs and CYP2C19 poor metabolizer status were associated with higher incidence of probable chronic migraine exclusively in men. Our results suggest a significant association between treatment with PPIs and migraine in this large population-based cohort and support a potential relevant role of gender and CYP2C19 phenotype.
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31.
  • Rukh, Gull, et al. (författare)
  • Dietary starch intake modifies the relation between copy number variation in the salivary amylase gene and BMI
  • 2017
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 106:1, s. 256-262
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies have shown conflicting associations between the salivary amylase gene (AMY1) copy number and obesity. Salivary amylase initiates starch digestion in the oral cavity; starch is a major source of energy in the diet. Objective: We investigated the association between AMY1 copy number and obesity traits, and the effect of the interaction between AMY1 copy number and starch intake on these obesity traits. Design: We first assessed the association between AMY1 copy number (genotyped by digital droplet polymerase chain reaction) and obesity traits in 4800 individuals without diabetes (mean age: 57 y; 60% female) from the Malmo "Diet and Cancer Cohort. Then we analyzed interactions between AMY1 copy number and energyadjusted starch intake (obtained by a modified diet history method) on body mass index (BMI) and body fat percentage. Results: AMY1 copy number was not associated with BMI (P = 0.80) or body fat percentage (P = 0.38). We observed a significant effect of the interaction between AMY1 copy number and starch intake on BMI (P-interaction = 0.007) and body fat percentage (P-interaction = 0.03). Upon stratification by dietary starch intake, BMI tended to decrease with increasing AMY1 copy numbers in the low-starch intake group (P = 0.07) and tended to increase with increasing AMY1 copy numbers in the high-starch intake group (P = 0.08). The lowest mean BMI was observed in the group of participants with a low AMY1 copy number and a high dietary intake of starch. Conclusions: Our findings suggest an effect of the interaction between starch intake and AMY1 copy number on obesity. Individuals with high starch intake but low genetic capacity to digest starch had the lowest BMI, potentially because larger amounts of undigested starch are transported through the gastrointestinal tract, contributing to fewer calories extracted from ingested starch.
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32.
  • Rukh, Gull, et al. (författare)
  • Effect of worry, depression, and sensitivity to environmental stress owing to neurotic personality on risk of cardiovascular disease : A Mendelian randomization study
  • 2023
  • Ingår i: Journal of personality. - : John Wiley & Sons. - 0022-3506 .- 1467-6494. ; 91:3, s. 856-867
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThis study investigated the putative causal link between neuroticism (using three genetically distinct subclusters namely depressed affect, worry, and sensitivity to environmental stress and adversity [SESA]) and cardiovascular disease (CVD).MethodA two-sample bi-directional Mendelian randomization (MR) approach was used. Genetic instruments were extracted from publically available GWAS summary statistics.ResultsIn forward MR analyses with neuroticism subclusters as exposures, no causal associations between worry or SESA cluster and any of the CVD traits were observed (p > .05 for all). However, a higher risk of having heart failure (odds ratio (95% confidence interval):1.32(1.12 to 1.56); p = .0011) and myocardial infarction (1.47[1.18 to 1.83]; p = 6.3 × 10-4) associated with depressed affect cluster was observed. In reverse MR analyses with CVD traits as exposures, no significant associations were observed (p > .05 for all).ConclusionsIndividuals with high neuroticism who are more susceptible to depressive symptoms are at higher risk for developing heart failure and myocardial infarction and should be more carefully evaluated for CVD risk in clinical settings. These individuals can potentially benefit from interventions aimed at reducing depressive symptoms to decrease CVD risk. There is no evidence to suggest that being sensitive to environmental stressors or being more worried can increase the risk for CVD.
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33.
  • Rukh, Gull, et al. (författare)
  • Evidence of a Causal Link Between the Well-Being Spectrum and the Risk of Myocardial Infarction : A Mendelian Randomization Study
  • 2022
  • Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiological studies have provided extensive evidence regarding the role of psychological risk factors in the pathogenesis of cardiovascular disease (CVD), but whether these associations are causal in nature is still unknown. We aimed to investigate whether the association between the wellbeing spectrum (WBS; derived from four psychological traits including life satisfaction, positive affect, neuroticism, and depressive symptoms) and CVD risk is causal. By employing a two-sample Mendelian randomization (MR) approach, the effect of the WBS on four CVD outcomes, including atrial fibrillation, heart failure, myocardial infarction, and ischemic stroke, was investigated. The genetically predicted WBS was associated with 38% lower risk for heart failure (odds ratio (OR): 0.62; 95% confidence interval [CI]: 0.50-0.78; P: 2.2 x 10(-5)) and 40% reduced risk of myocardial infarction (OR: 0.60; 95% CI: 0.47-0.78; P: 1.1 x 10(-4)). Of the WBS constituent traits, only depressive symptoms showed a positive causal association with heart failure and myocardial infarction. Neither WBS nor WBS constituent traits were associated with atrial fibrillation and ischemic stroke. In multivariable MR analyses, when genetic instruments for traditional CVD risk factors were also taken into consideration, the WBS was causally associated with a reduced risk for heart failure (OR: 0.72; 95% CI: 0.58-0.88; P: 0.001) and myocardial infarction (OR: 0.67; 95% CI: 0.52-0.86; P: 0.002). This study provides evidence that a higher WBS is causally associated with a decreased risk of developing CVD and, more specifically, myocardial infarction; moreover, the association is mainly driven by depressive symptoms. These results support current guidelines that suggest improving psychological wellbeing may help in reducing the burden of cardiovascular disease.
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34.
  • Rukh, Gull (författare)
  • Genetic Determinants of Obesity in Relation to Diet, Weight Gain and Mortality
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Obesity is one of the major health concerns that has reached epidemic proportions globally. It is generally believed to be a result of interactions between genetic and environmental factors. In this thesis we investigated the role of dietary factors in modifying the genetic susceptibility to obesity (papers I to III), studied the association between genetic susceptibility to obesity and weight gain at different time-points in life (paper IV) and tried to dissect the causality between cardiometabolic traits and mortality (paper V). The work in this thesis was conducted using data from the population based prospective Malmö Diet and Cancer Study (MDCS; N= ~30,000) and the Gene-Lifestyle interactions And Complex traits Involved in Elevated disease Risk (GLACIER; N= ~5000) cohorts. In paper I, we did not observe any evidence for macronutrient, fiber or total energy intake in modifying the genetic susceptibility to obesity when genetic susceptibility was represented as a Genetic Risk Score (GRS) based upon 13 BMI associated genetic variants. In individual SNP analyses, after correcting for multiple comparisons, some of the individual obesity loci such as NEGR1 rs2815752 associated with fat, carbohydrate and fiber intakes (P≤1x10-4 for all) and BDNF rs4923461 interacted with protein intake on BMI (Pinteraction=0.001). In paper II, pooled analyses of MDCS and GLACIER suggested 0.16 (SE=0.04) kg/m2 increase in BMI (P=8x10-5) in the lowest quartile of GRS (comprised of 30 BMI-associated genetic variants) for each increment in category of sugar-sweetened beverages (SSB) intake vs. 0.24 (SE=0.04) kg/m2 higher BMI in the highest GRS quartile (P=1x10-7). We also observed evidence for the role of SSB intake in modifying the genetic susceptibility to obesity (Pinteraction=0.049). In paper III, a copy number variant (CNV) in the salivary amylase gene (AMY1) did not associate with obesity traits neither in men nor in women (P>0.05 for all). However, upon stratification by dietary starch intake, BMI decreased with increasing AMY1 CNV in low starch intake group (P=0.035) and increased with increasing AMY1 CNV in the high starch intake group (P=0.04) among females. These results suggest a putative role of starch intake in modifying the association between AMY1 CNV and obesity in women (Pinteraction=0.041). In paper IV, a GRS based on 31 BMI-associated genetic variants was associated with increased annual weight change (β=0.003 kg; SE=0.01; P=7x10-8) and increased odds for substantial weight gain (OR=1.01; 95% CI= 1.00-1.02; P=0.013) per risk allele from young to middle age in MDCS. However, the GRS was associated with decreased annual weight change (β=-0.005 kg; SE=0.002; P=0.002) and decreased risk for substantial weight gain (OR=0.97; 95% CI= 0.96-0.99; P=0.001) per risk allele during and after middle-age in the pooled analyses of MDCS and GLACIER. These results suggest a paradoxical inversed relationship between genetic susceptibility to obesity and weight gain during and after middle age compared to increased weight gain in younger age. In paper V, observations from multivariable Mendelian randomization analyses suggest a direct causal association of TG (P=0.017 and P=0.028) and an inverse association of HDLC (P=0.049 and P=0.005) with total- and cardiovascular mortality, respectively. In conclusion, the results from this thesis suggest a role of specific dietary factors in modifying the genetic susceptibility to obesity and that genetic variation affect weight gain differently at different time-points in life but the underlying mechanisms need to be further understood. Additionally,our findings points towards causal associations between TG and HDLC and mortality which can help to devise better treatment strategies in clinical practice.
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35.
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36.
  • Rukh, Gull, et al. (författare)
  • Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malmö Diet and Cancer Study.
  • 2013
  • Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 8:6, s. 535-547
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene-environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malmö Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 × 10(-34)), fat mass (P = 6.3 × 10(-28)) and fat-free mass (P = 1.3 × 10(-24)). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 × 10(-4)). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.
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37.
  • Rukh, Gull, et al. (författare)
  • Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age
  • 2016
  • Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 40:2, s. 252-259
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/OBJECTIVE: Genome-wide-association studies have identified numerous body mass index (BMI)-associated variants, but it is unclear how these relate to weight gain in adults at different ages.METHODS: We examined the association of a genetic risk score (GRS), consisting of 31 BMI-associated variants, with an annual weight change (AWC) and a substantial weight gain (SWG) of 10% by comparing self-reported weight at 20 years (y) with baseline weight (mean: 58 y; s.d.: 8 y) in 21407 participants from the Malmö Diet and Cancer Study (MDCS), and comparing baseline weight to weight at follow-up (mean: 73 y; s.d.: 6 y) among 2673 participants. Association between GRS and AWG and SWG was replicated in 4327 GLACIER (Gene x Lifestyle interactions And Complex traits Involved in Elevated disease Risk) participants (mean: 45 y; s.d.: 7 y) with 10 y follow-up. Cohort-specific results were pooled by fixed-effect meta-analyses.RESULTS: In MDCS, the GRS was associated with increased AWC (β: 0.003; s.e: 0.01; P: 7 × 10(-8)) and increased odds for SWG (odds ratio (OR) 1.01 (95% confidence interval (CI): 1.00, 1.02); P: 0.013) per risk-allele from age 20y, but unexpectedly with decreased AWC (β: -0.006; s.e: 0.002; P: 0.009) and decreased odds for SWG OR 0.96 (95% CI: 0.93, 0.98); P: 0.001) between baseline and follow-up. Effect estimates from age 20 y to baseline differed significantly from those from baseline to follow-up (P: 0.0002 for AWC and P: 0.0001 for SWG). Similar to MDCS, the GRS was associated with decreased odds for SWG OR 0.98 (95% CI: 0.96, 1.00); P: 0.029) from baseline to follow-up in GLACIER. In meta-analyses (n=7000), the GRS was associated with decreased AWC (β: -0.005; s.e.m. 0.002; P: 0.002) and decreased odds for SWG OR 0.97 (95% CI: 0.96, 0.99); P: 0.001) per risk-allele.CONCLUSIONS: Our results provide convincing evidence for a paradoxical inversed relationship between a high number of BMI-associated risk-alleles and less weight gain during and after middle-age, in contrast to the expected increased weight gain seen in younger age.
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38.
  • Rukh, Gull, et al. (författare)
  • Personality, lifestyle and job satisfaction : causal association between neuroticism and job satisfaction using Mendelian randomisation in the UK biobank cohort
  • 2020
  • Ingår i: Translational Psychiatry. - : NATURE PUBLISHING GROUP. - 2158-3188. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Job-related stress has been associated with poor health outcomes but little is known about the causal nature of these findings. We employed Mendelian randomisation (MR) approach to investigate the causal effect of neuroticism, education, and physical activity on job satisfaction. Trait-specific genetic risk score (GRS) based on recent genome wide association studies were used as instrumental variables (IV) using the UK Biobank cohort (N = 315,536). Both single variable and multivariable MR analyses were used to determine the effect of each trait on job satisfaction. We observed a clear evidence of a causal association between neuroticism and job satisfaction. In single variable MR, one standard deviation (1 SD) higher genetically determined neuroticism score (4.07 units) was associated with -0.31 units lower job satisfaction (95% confidence interval (CI): -0.38 to -0.24; P = 9.5 x 10(-20)). The causal associations remained significant after performing sensitivity analyses by excluding invalid genetic variants from GRS(Neuroticism) (beta(95%CI): -0.28(-0.35 to -0.21); P = 3.4 x 10(-15)). Education (0.02; -0.08 to 0.12; 0.67) and physical activity (0.08; -0.34 to 0.50; 0.70) did not show any evidence for causal association with job satisfaction. When genetic instruments for neuroticism, education and physical activity were included together, the association of neuroticism score with job satisfaction was reduced by only -0.01 units, suggesting an independent inverse causal association between neuroticism score (P = 2.7 x 10(-17)) and job satisfaction. Our findings show an independent causal association between neuroticism score and job satisfaction. Physically active lifestyle may help to increase job satisfaction despite presence of high neuroticism scores. Our study highlights the importance of considering the confounding effect of negative personality traits for studies on job satisfaction.
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39.
  • Shungin, Dmitry, et al. (författare)
  • Using genetics to test the causal relationship of total adiposity and periodontitis : Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium
  • 2015
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 638-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI: 1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.
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40.
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41.
  • Stojkovic, Ivana, et al. (författare)
  • The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels
  • 2014
  • Ingår i: Genes and Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) associates with liver fat content and may lead to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and omega 6:omega 3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation have been reported. We examined interaction between rs738409 and overweight, and between rs738409 and dietary intakes (carbohydrates, sucrose and omega 6:omega 3-PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study-Cardiovascular Cohort, 4,827 individuals without diabetes aged 58 +/- 6 years, 2,346 with BMI <= 25 kg/m(2) and 2,478 with BMI > 25 kg/m(2), were included in cross-sectional analyses. Dietary data were collected by a modified diet history method. Overweight modified the association between rs738409 and fasting triglyceride levels (P-interaction = 0.003). G-allele associated with lower triglycerides only among overweight individuals (P = 0.01). Nominally, significant interaction on triglyceride levels was observed between rs738409 and sucrose among normal-weight individuals (P-interaction = 0.03). G-allele associated with lower triglycerides among overweight individuals in the lowest tertiles of carbohydrate and omega 6:omega 3-PUFA ratio (P = 0.04 and P = 0.001) and with higher triglycerides among normal-weight individuals in the highest tertile of sucrose (P = 0.001). We conclude that overweight and dietary sucrose may modify the association between rs738409 and fasting triglyceride levels.
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42.
  • Welander, Nike Zoe, et al. (författare)
  • Migraine and gastrointestinal disorders in middle and old age : A UK Biobank study
  • 2021
  • Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Migraine is a prevalent condition causing a substantial level of disability worldwide. Despite this, the pathophysiological mechanisms are not fully understood. Migraine often co-occurs with gastrointestinal disorders, but the direction of a potential causal link is unclear. The aim of this project was to investigate the associations between migraine and several gastrointestinal disorders in the same cohort in order to determine the relative strengths of these associations. Methods This cross-sectional study examined whether migraine is associated with irritable bowel syndrome (IBS), peptic ulcers, Helicobacter pylori (HP) infections, celiac disease, Crohn's disease and ulcerative colitis. Baseline data covering 489,753 UK Biobank participants (migraine group: n = 14,180) were analyzed using Pearson's chi-square tests and adjusted binary logistic regression models. Results Migraine was significantly associated with IBS (odds ratio [OR] 2.24, 95% confidence interval [CI] 2.08-2.40, p <.001) and peptic ulcers (OR 1.55, 95% CI 1.35-1.77, p <.001). Migraine was not associated with HP infection (OR 1.34, 95% CI 1.04-1.73, p = .024), celiac disease (OR 1.29, 95% CI 1.04-1.60, p = .023), Crohn's disease (OR 1.08, 95% CI 0.80-1.45, p = .617) or ulcerative colitis (OR 1.00, 95% CI 0.79-1.27, p = .979) after adjusting for multiple testing. Conclusions Migraine was associated with IBS and peptic ulcers in this large population-based cohort. The associations with HP infection, celiac disease, Crohn's disease, and ulcerative colitis did not reach significance, suggesting a weaker link between migraine and autoimmune gastrointestinal conditions or HP infection.
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43.
  • Welander, Nike Zoe, et al. (författare)
  • Migraine, inflammatory bowel disease and celiac disease : A Mendelian randomization study
  • 2023
  • Ingår i: Headache. - : John Wiley & Sons. - 0017-8748 .- 1526-4610. ; 63:5, s. 642-651
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BACKGROUND: Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.METHODS: Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.RESULTS: Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99-1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99-1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96-1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79-1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00-1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92-0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02-1.29, p = 0.025). However, the results were not significant after multiple testing correction.CONCLUSIONS: We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.
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