| 1. |
- Gielen, Marij, et al.
(författare)
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Body mass index is negatively associated with telomere length : A collaborative cross-sectional meta-analysis of 87 observational studies
- 2018
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 108:3, s. 453-475
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Tidskriftsartikel (refereegranskat)abstract
- Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
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| 2. |
- Jochumsen, Sara, et al.
(författare)
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Physical activity during pregnancy and intelligence in sons; A cohort study
- 2019
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 29:12, s. 1988-1995
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to examine the association between exercise during pregnancy and intelligence score in offspring. We analyzed data from 4008 women from the Aarhus Birth Cohort, Aarhus University Hospital, Denmark, recruited during pregnancy from July 1989 to November 1991 and their sons who were registered at conscription at 17-20 years of age. The women gave information by self-administered questionnaires during the first trimester including leisure-time physical activity and weekly hours of sport. This information was linked to the sons’ measures of intelligence by Børge Priens test scores from the Danish Conscription Registry. Only sons were included since very few women register at conscription in Denmark. The main outcome measure was the Børge Priens test score as a continuous variable and with a low score defined as <10% of the population score. Analyses were adjusted for maternal body mass index, years in school, and smoking. Sons of women with light and moderate to heavy leisure-time physical activity had lower risk of having a low intelligence score compared with sons of women with sedentary activity: adjusted odds ratio (aOR) 0.66 (95% CI 0.49;0.88) and 0.46 (95% CI 0.23;0.93), respectively. Furthermore, sons of women engaged in sports had lower risk of a low intelligence score: aOR 0.50 (95% CI 0.30; 0.83) for 1-2 h/wk and 0.62 (95% CI 0.35; 1.10) for ≥3 h/wk compared with no weekly sports activity. In conclusion, a higher level of physical activity during pregnancy was associated with a lower risk of low intelligence score in early adulthood in sons.
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| 3. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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