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Genetic risk factors for BMI and obesity in an ethnically diverse population: results from the population architecture using genomics and epidemiology (PAGE) study.

TitleGenetic risk factors for BMI and obesity in an ethnically diverse population: results from the population architecture using genomics and epidemiology (PAGE) study.
Publication TypeJournal Article
Year of Publication2013
AuthorsFesinmeyer MD, North KE, Ritchie MD, Lim U, Franceschini N, Wilkens LR, Gross MD, Bůžková P, Glenn K, P Quibrera M, Fernández-Rhodes L, Li Q, Fowke JH, Li R, Carlson CS, Prentice RL, Kuller LH, Manson JAE, Matise TC, Cole SA, Chen CTL, Howard BV, Kolonel LN, Henderson BE, Monroe KR, Crawford DC, Hindorff LA, Buyske S, Haiman CA, Le Marchand L
Secondary AuthorsPeters U
JournalObesity (Silver Spring)
Volume21
Issue4
Pagination835-46
Date Published2013 Apr
ISSN1930-739X
KeywordsAlleles, Body Mass Index, Ethnic Groups, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Metagenomics, Obesity, Phenotype, Polymorphism, Single Nucleotide, Risk Factors
Abstract

OBJECTIVE: Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups.

DESIGN AND METHODS: As part of the "Population Architecture using Genomics and Epidemiology (PAGE)" Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined "replicating SNPs" (in European Americans) and "generalizing SNPs" (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI.

RESULTS: By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians.

CONCLUSION: Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.

DOI10.1002/oby.20268
Alternate JournalObesity (Silver Spring)
PubMed ID23712987
PubMed Central IDPMC3482415
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
U01HG004802 / HG / NHGRI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States
U01HG004798 / HG / NHGRI NIH HHS / United States
U01HG004801 / HG / NHGRI NIH HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
P30 CA071789 / CA / NCI NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States