Genome-wide population-based association study of extremely overweight young adults - the GOYA study

Paternoster, Lavinia, Evans, David M., Aagaard Nohr, Ellen, Holst, Claus, Gaborieau, Valerie, Brennan, Paul, Prior Gjesing, Anette, Grarup, Niels, Witte, Daniel R., Jorgensen, Torben, Linneberg, Allan, Lauritzen, Torsten, Sandbaek, Anelli, Hansen, Torben, Pedersen, Oluf, Elliott, Katherine S., Kemp, John P., St. Pourcain, Beate, McMahon, George, Zelenika, Diana, Hager, Jorg, Lathrop, Mark, Timpson, Nicholas J., Smith, George Davey and Sorensen, Thorkild I. A. (2011) Genome-wide population-based association study of extremely overweight young adults - the GOYA study. PLoS One, 6 9: e24303.1-e24303.9. doi:10.1371/journal.pone.0024303

Author Paternoster, Lavinia
Evans, David M.
Aagaard Nohr, Ellen
Holst, Claus
Gaborieau, Valerie
Brennan, Paul
Prior Gjesing, Anette
Grarup, Niels
Witte, Daniel R.
Jorgensen, Torben
Linneberg, Allan
Lauritzen, Torsten
Sandbaek, Anelli
Hansen, Torben
Pedersen, Oluf
Elliott, Katherine S.
Kemp, John P.
St. Pourcain, Beate
McMahon, George
Zelenika, Diana
Hager, Jorg
Lathrop, Mark
Timpson, Nicholas J.
Smith, George Davey
Sorensen, Thorkild I. A.
Title Genome-wide population-based association study of extremely overweight young adults - the GOYA study
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-09-15
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pone.0024303
Open Access Status DOI
Volume 6
Issue 9
Start page e24303.1
End page e24303.9
Total pages 9
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
Abstract Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ~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 ~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<5×10 -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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID WT 084762MA
MRC G0800582
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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