| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- Craig, Wendy, et al.
(författare)
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Social Media Use and Cyber-Bullying: A Cross-National Analysis of Young People in 42 Countries
- 2020
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Ingår i: Journal of Adolescent Health. - : Elsevier BV. - 1054-139X .- 1879-1972. ; 66:6, s. S100-S108
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Social media use (SMU) has become an intrinsic part of adolescent life. Negative consequences of SMU for adolescent health could include exposures to online forms of aggression. We explored age, gender, and cross-national differences in adolescents' engagement in SMU, then relationships between SMU and victimization and the perpetration of cyber-bullying. Methods: We used data on young people aged 11–15 years (weighted n = 180,919 in 42 countries) who participated in the 2017–2018 Health Behaviour in School-aged Children study to describe engagement in the three types of SMU (intense, problematic, and talking with strangers online) by age and gender and then in the perpetration and victimization of cyber-bullying. Relationships between SMU and cyber-bullying outcomes were estimated using Poisson regression (weighted n = 166,647 from 42 countries). Results: Variations in SMU and cyber-bullying follow developmental and gender-based patterns across countries. In pooled analyses, engagement in SMU related to cyber-bullying victimization (adjusted relative risks = 1.14 [95% confidence interval (CI): 1.10–1.19] to 1.48 [95% CI: 1.42–1.55]) and perpetration (adjusted relative risk = 1.31 [95% CI: 1.26–1.36] to 1.84 [95% CI: 1.74–1.95]). These associations were stronger for cyber-perpetration versus cyber-victimization and for girls versus boys. Problematic SMU was most strongly and consistently associated with cyber-bullying, both for victimization and perpetration. Stratified analyses showed that SMU related to cyber-victimization in 19%–45% of countries and to cyber-perpetration in 38%–86% of countries. Conclusions: Accessibility to social media and its pervasive use has led to new opportunities for online aggression. The time adolescents spend on social media, engage in problematic use, and talk to strangers online each relate to cyber-bullying and merit public health intervention. Problematic use of social media poses the strongest and most consistent risk.
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| 3. |
- Palmer, C. N. A., et al.
(författare)
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Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D). The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity. Methods and Findings: PNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n = 3,473) and in the Go-DARTS (n = 15,448), a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P = 0.040) and in severely obese individuals in the Go-DARTS study (O. R. 1.37, 95% C.I. 1.13-1.66, P = 0.001). The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35) individuals in the Go-DARTS study (P for interaction = 0.002). This provides evidence for the obesity interaction with 148M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study. Conclusions: Severely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity-driven hepatic lipid accumulation may contribute to T2D susceptibility.
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| 4. |
- Postmus, Iris, et al.
(författare)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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