| 1. |
- Ciuculete, Diana-Maria, et al.
(author)
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A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score
- 2017
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In: Translational Psychiatry. - : NATURE PUBLISHING GROUP. - 2158-3188. ; 7
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with psychiatric diseases. Increasing body of evidence suggests a complex connection of SNPs and the transcriptional and epigenetic regulation of gene expression, which is poorly understood. In the current study, we investigated the interplay between genetic risk variants, shifts in methylation and mRNA levels in whole blood from 223 adolescents distinguished by a risk for developing psychiatric disorders. We analyzed 37 SNPs previously associated with psychiatric diseases in relation to genome-wide DNA methylation levels using linear models, with Bonferroni correction and adjusting for cell-type composition. Associations between DNA methylation, mRNA levels and psychiatric disease risk evaluated by the Development and Well-Being Assessment (DAWBA) score were identified by robust linear models, Pearson's correlations and binary regression models. We detected five SNPs (in HCRTR1, GAD1, HADC3 and FKBP5) that were associated with eight CpG sites, validating five of these SNP-CpG pairs. Three of these CpG sites, that is, cg01089319 (GAD1), cg01089249 (GAD1) and cg24137543 (DIAPH1), manifest in significant gene expression changes and overlap with active regulatory regions in chromatin states of brain tissues. Importantly, methylation levels at cg01089319 were associated with the DAWBA score in the discovery group. These results show how distinct SNPs linked with psychiatric diseases are associated with epigenetic shifts with relevance for gene expression. Our findings give a novel insight on how genetic variants may modulate risks for the development of psychiatric diseases.
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| 2. |
- Gentreau, Mélissa, et al.
(author)
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The effects of statins on cognitive performance are mediated by low-density lipoprotein, C-reactive protein and blood glucose concentrations.
- 2023
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X.
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Journal article (peer-reviewed)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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| 3. |
- Boström, Adrian, et al.
(author)
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A MIR4646 associated methylation locus is hypomethylated in adolescent depression
- 2017
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In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 220, s. 117-128
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Journal article (peer-reviewed)abstract
- Background: Studies of epigenetics and transcriptional activity in adolescents may provide knowledge about possible preventive strategies of depression. Methods: We present a methylome-wide association study (MWAS) and cohort validation analysis of depression in adolescents, in two separate cohorts: discovery (n = 93) and validation data set 1 (n = 78). The genome-wide methylation pattern was measured from whole blood using the Illumina 450K array. A second validation cohort, validation data set 2, consists of post-mortem brain biopsies from depressed adults (n = 58). We performed a MWAS by robust multiple linear regressions of methylation to a modified risk-score assessment of depression. Methylation levels of candidate CpG sites were correlated with expression levels of the associated gene in an independent cohort of 11 healthy volunteers. Results: The methylation state of two CpG sites reliably predicted ratings of depression in adolescents (cg13227623 and cg04102384) (p < 10E-06). Cohort validation analysis confirmed cg04102384 - located in the promoter region of microRNA 4646 (MIR4646) - to be hypomethylated in both validation data set 1 and validation data set 2 (p < 0.05). Cg04102384 was inversely correlated to expression levels of MIR4646-3p in healthy controls (p < 0.05). Limitations: MIR4646 was not differentially expressed in a subset of samples with adolescent depression measured by qRT-PCR measurements. Conclusion: We identify a specific MIR4646 associated epigenetic risk site to be associated with depression in adolescents. Cg04102384 putatively regulates gene expression of MIR4646-3p. Target gene prediction and gene set overrepresentation analysis revealed involvement of this miRNA in fatty acid elongation, a process related to omega-3 fatty acids, previously associated with depression.
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| 4. |
- Brooks, Samantha J., et al.
(author)
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Important gender differences in psychosomatic and school-related complaints in relation to adolescent weight status
- 2021
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Journal article (peer-reviewed)abstract
- Underweight or overweight in adolescence is linked to several adverse health outcomes. Less evidence exists about the association between weight status and school-related psychosocial characteristics in high income countries. We sought to investigate the relationship between weight status and psychosomatic and school-related complaints with a focus on gender differences. The study is a cohort of 18,462 adolescents (12-19 years; 51% girls) conducted in Sweden. The associations between weight status and psychosomatic and school-related complaints were estimated by binary logistic regression adjusted for several potential confounders. After correction for multiple testing, being underweight or overweight/obese was adversely associated with several psychosomatic and school-related complaints with significant differences between boys and girls. Specifically, underweight boys had higher odds to have psychosomatic complaints than normal-weight boys, while no such associations were observed among underweight girls. Overweight/obese (vs. normal-weight) boys had higher odds to complain about headache, pain in the back/hips, and feeling low. Overweight/obese (vs. normal-weight) girls were more likely to complain about feeling low, anxious/worried and having difficulty in falling asleep (P <= 0.01). In relation to school-related complaints (e.g., being bullied at school and academic failure), greater associations were observed for overweight/obese girls and boys than for underweight adolescents compared with normal-weight peers.
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| 5. |
- Brooks, Samantha J., et al.
(author)
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Self-Reported Psychosomatic Complaints and Conduct Problems in Swedish Adolescents
- 2022
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In: Children. - : MDPI AG. - 2227-9067. ; 9:7
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Journal article (peer-reviewed)abstract
- Physical conditions in children and adolescents are often under reported during mainstream school years and may underlie mental health disorders. Additionally, comparisons between younger and older schoolchildren may shed light on developmental differences regarding the way in which physical conditions translate into conduct problems. The aim of the current study was to examine the incidence of psychosomatic complaints (PSC) in young and older adolescent boys and girls who also report conduct problems. A total of 3132 Swedish adolescents (age range 15-18 years, 47% boys) completed the Uppsala Life and Health Cross-Sectional Survey (LHS) at school. The LHS question scores were categorised by two researchers who independently identified questions that aligned with DSM-5 conduct disorder (CD) criteria and PSC. MANOVA assessed the effects of PSC, age, and gender on scores that aligned with the DSM criteria for CD. The main effects of gender, age, and PSC on the conduct problem scores were observed. Adolescents with higher PSC scores had higher conduct problem scores. Boys had higher serious violation of rules scores than girls, particularly older boys with higher PSC scores. Psychosomatic complaints could be a useful objective identifier for children and adolescents at risk of developing conduct disorders. This may be especially relevant when a reliance on a child's self-reporting of their behavior may not help to prevent a long-term disturbance to their quality of life.
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| 6. |
- Miguet, Maud, et al.
(author)
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Important Difference between Occupational Hazard Exposure among Shift Workers and Other Workers; Comparing Workplace before and after 1980
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:20
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Journal article (peer-reviewed)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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| 7. |
- Olivo, Gaia, et al.
(author)
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Resting-State Bra in and the FTO Obesity Risk Allele : Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes
- 2016
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In: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 10
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Journal article (peer-reviewed)abstract
- Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.
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| 8. |
- Tan, Xiao, et al.
(author)
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Association Between Self-Reported Sleep Duration and Body Composition in Middle-Aged and Older Adults
- 2019
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In: Journal of Clinical Sleep Medicine (JCSM). - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 15:3, s. 431-435
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Journal article (peer-reviewed)abstract
- STUDY OBJECTIVES: The current study sought to examine whether self-reported sleep duration is linked to an adverse body composition in 19,709 adults aged 45 to 75 years. METHODS: All variables used in the current study were derived from the Swedish EpiHealth cohort study. Habitual sleep duration was measured by questionnaires. Body composition was assessed by bioimpedance. The main outcome variables were fat mass and fat-free mass (in kg). Analysis of covariance adjusting for age, sex, fat mass in the case of fat-free mass (and vice versa), leisure time physical activity, smoking, and alcohol consumption was used to investigate the association between sleep duration and body composition. RESULTS: Short sleep (defined as ≤ 5 hours sleep per day) and long sleep (defined as 8 or more hours of sleep per day) were associated with lower fat-free mass and higher fat mass, compared with 6 to 7 hours of sleep duration (P < .05). CONCLUSIONS: These observations could suggest that both habitual short and long sleep may contribute to two common clinical phenotypes in middle-aged and older humans, ie, body adiposity and sarcopenia. However, the observational nature of our study does not allow for causal interpretation.
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| 9. |
- Titova, Olga E, et al.
(author)
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Anger frequency and risk of cardiovascular morbidity and mortality
- 2022
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In: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:4, s. 1-8
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Journal article (peer-reviewed)abstract
- Aims: Anger may increase the risk of cardiovascular diseases (CVDs) but previous findings are inconclusive and large prospective studies are needed. We investigated whether frequency of strong anger is associated with the incidence of specific CVDs and CVD mortality, and if sex, age, and cardiometabolic risk factors modify these associations.Methods and results: We used data from a population-based cohort of 47 077 Swedish adults (56-94 years of age) who completed questionnaires regarding their experience of anger, lifestyle habits, and health characteristics. Participants were followed for incident cardiovascular outcomes and death up to 9 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios and confidence intervals adjusted for potential confounders were assessed.In multivariable analyses, frequent episodes of strong anger were associated with an increased risk of heart failure, atrial fibrillation, and CVD mortality [hazard ratios (95% confidence intervals) = 1.19 (1.04-1.37), 1.16 (1.06-1.28), and 1.23 (1.09-1.40), respectively]. The link between anger frequency and heart failure was more pronounced in men and participants with a history of diabetes. No evidence of an independent association of anger frequency with risk of myocardial infarction, aortic valve stenosis, and abdominal aortic aneurysm was found.Conclusion: Our findings indicate that anger may contribute to the development of specific CVDs and CVD mortality, especially heart failure in men and in those with diabetes.
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| 10. |
- Titova, Olga E, et al.
(author)
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Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions : a meta-analysis of VBM studies
- 2013
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In: BMC Psychiatry. - 1471-244X. ; 13:1, s. 110-
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Journal article (peer-reviewed)abstract
- BACKGROUNDStructural imaging studies demonstrate brain tissue abnormalities in eating disorders, yet a quantitative analysis has not been done.METHODSIn global and regional meta-analyses of 9 voxel-based morphometry (VBM) studies, with a total of 228 eating disorder participants (currently ill with anorexia nervosa), and 240 age-matched healthy controls, we compare brain volumes using global and regional analyses.RESULTSAnorexia nervosa (AN) patients have global reductions in gray (effect size = -0.66) and white matter (effect size = -0.74) and increased cerebrospinal fluid (effect size = 0.98) and have regional decreases in left hypothalamus, left inferior parietal lobe, right lentiform nucleus and right caudate, and no significant increases. No significant difference in hemispheric lateralization was found.CONCLUSIONSGlobal and regional meta-analyses suggest that excessive restrained eating as found in those with anorexia nervosa coincides with structural brain changes analogous to clinical symptoms.
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