Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults - The GOYA Study

被引：85

作者：

Paternoster, Lavinia ^{[1
,2
]}

Evans, David M. ^{[1
,2
]}

Nohr, Ellen Aagaard ^{[3
]}

Holst, Claus ^{[4
]}

Gaborieau, Valerie ^{[5
]}

Brennan, Paul ^{[5
]}

Gjesing, Anette Prior ^{[6
]}

Grarup, Niels ^{[6
]}

Witte, Daniel R. ^{[8
]}

Jorgensen, Torben ^{[9
]}

Linneberg, Allan ^{[9
]}

Lauritzen, Torsten ^{[10
]}

Sandbaek, Anelli ^{[10
]}

Hansen, Torben ^{[6
,7
]}

Pedersen, Oluf ^{[6
,11
,12
]}

Elliott, Katherine S. ^{[13
]}

Kemp, John P. ^{[1
,2
]}

St Pourcain, Beate ^{[2
]}

McMahon, George ^{[1
,2
]}

Zelenika, Diana ^{[14
]}

Hager, Joerg ^{[14
]}

Lathrop, Mark ^{[14
,15
]}

Timpson, Nicholas J. ^{[1
,2
]}

Smith, George Davey ^{[1
,2
]}

Sorensen, Thorkild I. A. ^{[4
]}

机构：

[1] Univ Bristol, MRC CAiTE Ctr, Bristol, Avon, England

[2] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[3] Aarhus Univ, Inst Publ Hlth, Aarhus, Denmark

[4] Copenhagen Univ Hosp, Inst Prevent Med, Copenhagen, Denmark

[5] IARC, Lyon, France

[6] Univ Copenhagen, Novo Nordisk Ctr Metab Res, Fac Hlth Sci, Copenhagen, Denmark

[7] Univ So Denmark, Fac Hlth Sci, Odense, Denmark

[8] Steno Diabet Ctr, Copenhagen, Denmark

[9] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark

[10] Univ Aarhus, Dept Gen Practice, Aarhus, Denmark

[11] Univ Copenhagen, Inst Biomed Sci, Fac Hlth Sci, Copenhagen, Denmark

[12] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark

[13] Wellcome Trust Ctr Human Genet, Oxford, England

[14] Ctr Natl Genotypage, Evry, France

[15] CEPH, Fdn Jean Dausset, Paris, France

来源：

PLOS ONE | 2011年 / 6卷 / 09期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

QUANTITATIVE-TRAIT LOCI; LINKAGE DISEQUILIBRIUM; OBESITY; VARIANTS; DETECT; POWER; RISK;

D O I：

10.1371/journal.pone.0024303

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

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