期刊
PLOS ONE
卷 6, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0024303
关键词
-
资金
- Novo Nordisk
- Novo Nordisk Scandinavia
- Astra Denmark
- Pfizer Denmark
- GlaxoSmithKline Pharma Denmark
- Servier Denmark
- HemoCue Denmark
- Wellcome Trust [WT 084762MA, 076467, WT083431MA]
- Medical Council New Investigator [MRC G0800582]
- INCa, France
- Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LuCAMP)
- Novo Nordisk Foundation
- UK Medical Research Council [74882]
- University of Bristol
- Medical Research Council [G0600705, G0800582] Funding Source: researchfish
- MRC [G0800582, G0600705] Funding Source: UKRI
Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining,similar to 1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations. Methodology/Principal Findings: From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing similar to 212,000 individuals). We followed up novel (at the time of the study) association signals (p<0.001) from the discovery cohort in a genome-wide study of 5,846 Europeans, before attempting to replicate the most strongly associated 28 SNPs in an independent sample of Danish individuals (n = 20,917) and a population-based cohort of 15-year-old British adolescents (n = 2,418). Our discovery analysis identified SNPs at three loci known to be associated with BMI with genome-wide confidence (P<5 x 10(-8); FTO, MC4R and FAIM2). We also found strong evidence of association at the known TMEM18, GNPDA2, SEC16B, TFAP2B, SH2B1 and KCTD15 loci (p<0.001), and nominal association (p<0.05) at a further 8 loci known to be associated with BMI. However, meta-analyses of our discovery and replication cohorts identified no novel associations. Significance: Our results indicate that the detectable genetic variation associated with extreme overweight is very similar to that previously found for general BMI. This suggests that population-based study designs with enriched sampling of individuals with the extreme phenotype may be an efficient method for identifying common variants that influence quantitative traits and a valid alternative to genotyping all individuals in large population-based studies, which may require tens of thousands of subjects to achieve similar power.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据