Common body mass index-associated variants confer risk of extreme obesity
Open Access
- 24 June 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 18 (18), 3502-3507
- https://doi.org/10.1093/hmg/ddp292
Abstract
To investigate the genetic architecture of severe obesity, we performed a genome-wide association study of 775 cases and 3197 unascertained controls at ∼550 000 markers across the autosomal genome. We found convincing association to the previously described locus including the FTO gene. We also found evidence of association at a further six of 12 other loci previously reported to influence body mass index (BMI) in the general population and one of three associations to severe childhood and adult obesity and that cases have a higher proportion of risk-conferring alleles than controls. We found no evidence of homozygosity at any locus due to identity-by-descent associating with phenotype which would be indicative of rare, penetrant alleles, nor was there excess genome-wide homozygosity in cases relative to controls. Our results suggest that variants influencing BMI also contribute to severe obesity, a condition at the extreme of the phenotypic spectrum rather than a distinct condition.Keywords
This publication has 18 references indexed in Scilit:
- Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populationsNature Genetics, 2009
- Genome-wide association yields new sequence variants at seven loci that associate with measures of obesityNature Genetics, 2008
- Six new loci associated with body mass index highlight a neuronal influence on body weight regulationNature Genetics, 2008
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006
- Genetics of obesityPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2006
- A Fine-Scale Map of Recombination Rates and Hotspots Across the Human GenomeScience, 2005
- Assessing the impact of population stratification on genetic association studiesNature Genetics, 2004
- Estimation of the Inbreeding Coefficient through Use of Genomic DataAmerican Journal of Human Genetics, 2003
- Genomic Control for Association StudiesBiometrics, 1999
- Monte Carlo likelihood in the genetic mapping of complex traitsPhilosophical Transactions Of The Royal Society B-Biological Sciences, 1994