| 1. |
- Ahmad, Shafqat, et al.
(författare)
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Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome : A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study
- 2022
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 71:2, s. 329-339
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.
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| 2. |
- Ahmad, Shafqat, et al.
(författare)
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Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607-
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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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| 3. |
- Dawes, Christopher T, et al.
(författare)
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The Relationship Between Genes, Psychological Traits, and Political Participation
- 2014
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Ingår i: American Journal of Political Science. - : Wiley-Blackwell. - 0092-5853 .- 1540-5907. ; 58:4, s. 888-903
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Tidskriftsartikel (refereegranskat)abstract
- Recent research demonstrates that a wide range of political attitudes, beliefs, and behaviors canbe explained in part by genetic variation. However, these studies have not yet identied themechanisms that generate such a relationship. Some scholars have speculated that psychologicaltraits mediate the relationship between genes and political participation, but so far there havebeen no empirical tests. Here we focus on the role of three psychological traits that are believed toinuence political participation: cognitive ability, personal control, and extraversion. Utilizinga unique sample of more than 2,000 Swedish twin pairs, we show that a common genetic factorcan explain most of the relationship between these psychological traits and acts of politicalparticipation as well as predispositions related to participation. While our analysis is not adenitive test, our results suggest an upper bound for a proposed mediation relationship betweengenes, psychological traits, and political participation.
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| 4. |
- Hatemi, Peter, et al.
(författare)
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Genetic Influences on Political Ideologies : Twin Analyses of 19 Measures of Political Ideologies from Five Democraciesand Genome-Wide Findings from Three Populations
- 2014
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Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 44:3, s. 282-294
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Tidskriftsartikel (refereegranskat)abstract
- Almost 40 years ago, evidence from large studies of adult twins and their relatives suggested that between 30 and 60 % of the variance in social and political attitudes could be explained by genetic influences. However, these findings have not been widely accepted or incorporated into the dominant paradigms that explain the etiology of political ideology. This has been attributed in part to measurement and sample limitations, as well the relative absence of molecular genetic studies. Here we present results from original analyses of a combined sample of over 12,000 twins pairs, ascertained from nine different studies conducted in five democracies, sampled over the course of four decades. We provide evidence that genetic factors play a role in the formation of political ideology, regardless of how ideology is measured, the era, or the population sampled. The only exception is a question that explicitly uses the phrase “Left–Right”. We then present results from one of the first genome-wide association studies on political ideology using data from three samples: a 1990 Australian sample involving 6,894 individuals from 3,516 families; a 2008 Australian sample of 1,160 related individuals from 635 families and a 2010 Swedish sample involving 3,334 individuals from 2,607 families. No polymorphisms reached genome-wide significance in the meta-analysis. The combined evidence suggests that political ideology constitutes a fundamental aspect of one’s genetically informed psychological disposition, but as Fisher proposed long ago, genetic influences on complex traits will be composed of thousands of markers of very small effects and it will require extremely large samples to have enough power in order to identify specific polymorphisms related to complex social traits.
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| 5. |
- Hong, Mun-Gwan, et al.
(författare)
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Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality
- 2020
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 3:10, s. e202000817-
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Tidskriftsartikel (refereegranskat)abstract
- Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50–92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10−6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12–1.39; P = 6.45 × 10−5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7–9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.
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| 6. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 7. |
- Li, Xia, et al.
(författare)
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Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up.
- 2020
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Biological age measurements (BAs) assess aging-related physiological change and predict health risks among individuals of the same chronological age (CA). Multiple BAs have been proposed and are well studied individually but not jointly. We included 845 individuals and 3973 repeated measurements from a Swedish population-based cohort and examined longitudinal trajectories, correlations, and mortality associations of nine BAs across 20 years follow-up. We found the longitudinal growth of functional BAs accelerated around age 70; average levels of BA curves differed by sex across the age span (50-90 years). All BAs were correlated to varying degrees; correlations were mostly explained by CA. Individually, all BAs except for telomere length were associated with mortality risk independently of CA. The largest effects were seen for methylation age estimators (GrimAge) and the frailty index (FI). In joint models, two methylation age estimators (Horvath and GrimAge) and FI remained predictive, suggesting they are complementary in predicting mortality.
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| 8. |
- Liu, Qianwei, et al.
(författare)
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Cardiovascular Diseases And Psychiatric Disorders During The Diagnostic Workup Of Suspected Hematological Malignancy
- 2019
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 11, s. 1025-1034
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little attention has been given to the risk of cardiovascular and psychiatric comorbidities during the clinical evaluation of a suspected hematological malignancy.Methods: Based on Skåne Healthcare Register, we performed a population-based cohort study of 1,527,449 individuals residing during 2005-2014 in Skåne, Sweden. We calculated the incidence rate ratios (IRRs) of cardiovascular diseases or psychiatric disorders during the diagnostic workup of 5495 patients with hematological malignancy and 18,906 individuals that underwent a bone marrow aspiration or biopsy or lymph node biopsy without receiving a diagnosis of any malignancy ("biopsied individuals"), compared to individuals without such experience (i.e., reference).Results: There was a higher rate of cardiovascular diseases during the diagnostic workup of patients with hematological malignancy (overall IRR, 3.3; 95% CI, 2.9 to 3.8; greatest IRR for embolism and thrombosis, 8.1; 95% CI, 5.2 to 12.8) and biopsied individuals (overall IRR, 4.9; 95% CI, 4.6 to 5.3; greatest IRR for stroke, 37.5; 95% CI, 34.1 to 41.2), compared to reference. Similarly, there was a higher rate of psychiatric disorders during the diagnostic workup of patients with hematological malignancy (IRR, 2.1; 95% CI, 1.5 to 2.8) and biopsied individuals (IRR, 3.1; 95% CI, 2.9 to 3.4). The rate increases were greater around the time of diagnosis or biopsy, compared to thereafter, for both outcomes.Conclusion: There were higher rates of cardiovascular diseases and psychiatric disorders during the diagnostic workup of a suspected hematological malignancy, regardless of the final diagnosis.
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| 9. |
- Mosing, Miriam A, et al.
(författare)
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Genetic and environmental influences on the relationship between flow proneness, locus of control and behavioral inhibition
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:11, s. e47958-
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Tidskriftsartikel (refereegranskat)abstract
- Flow is a psychological state of high but subjectively effortless attention that typically occurs during active performance of challenging tasks and is accompanied by a sense of automaticity, high control, low self-awareness, and enjoyment. Flow proneness is associated with traits and behaviors related to low neuroticism such as emotional stability, conscientiousness, active coping, self-esteem and life satisfaction. Little is known about the genetic architecture of flow proneness, behavioral inhibition and locus of control - traits also associated with neuroticism - and their interrelation. Here, we hypothesized that individuals low in behavioral inhibition and with an internal locus of control would be more likely to experience flow and explored the genetic and environmental architecture of the relationship between the three variables. Behavioral inhibition and locus of control was measured in a large population sample of 3,375 full twin pairs and 4,527 single twins, about 26% of whom also scored the flow proneness questionnaire. Findings revealed significant but relatively low correlations between the three traits and moderate heritability estimates of .41, .45, and .30 for flow proneness, behavioral inhibition, and locus of control, respectively, with some indication of non-additive genetic influences. For behavioral inhibition we found significant sex differences in heritability, with females showing a higher estimate including significant non-additive genetic influences, while in males the entire heritability was due to additive genetic variance. We also found a mainly genetically mediated relationship between the three traits, suggesting that individuals who are genetically predisposed to experience flow, show less behavioral inhibition (less anxious) and feel that they are in control of their own destiny (internal locus of control). We discuss that some of the genes underlying this relationship may include those influencing the function of dopaminergic neural systems.
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| 10. |
- Song, Huan, et al.
(författare)
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Loss of a co-twin at birth and subsequent risk of psychiatric disorders
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Twins suffering a co-twin loss at birth have reported feelings of loneliness and grief while it remains unexplored if they suffer increased risk of psychiatric disorders. We contrasted rate of first-onset psychiatric disorders among all Swedish-born twins whose co-twin died within 60 days after birth between 1973 and 2011 (n = 787) to that of 3935 matched unexposed twins, 3935 matched singletons (both matched to the exposed twins by birth year, sex, and birth characteristics), and 880 full siblings of the exposed twins. During a median of 19-year follow-up, exposed twins were at increased risk of first-onset psychiatric disorders (hazard ratio = 1.56, 95%CI 1.30-1.87) compared with unexposed twins. We observed the strongest association for emotional disorders and for psychiatric disorders diagnosed before the age of 25. Comparisons with matched singletons and the twin's full siblings rendered similar results, corroborating an association of loss of a co-twin at birth with subsequent risk of psychiatric disorders.
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