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Admixture mapping of obesity-related traits in African Americans: the Atherosclerosis Risk in Communities (ARIC) Study.

TitleAdmixture mapping of obesity-related traits in African Americans: the Atherosclerosis Risk in Communities (ARIC) Study.
Publication TypeJournal Article
Year of Publication2010
AuthorsCheng C-Y, Reich D, Coresh J, Boerwinkle E, Patterson N, Li M, North KE, Tandon A, Bailey-Wilson JE, Wilson JG, Kao LWH
JournalObesity (Silver Spring)
Volume18
Issue3
Pagination563-72
Date Published2010 Mar
ISSN1930-739X
KeywordsAfrican Americans, Atherosclerosis, Body Composition, Body Mass Index, Body Weight, Chromosome Mapping, Chromosomes, Human, Pair 2, European Continental Ancestry Group, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Obesity, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Skinfold Thickness, Waist Circumference
Abstract

Obesity is an important cause of morbidity and mortality worldwide. In the United States, the prevalence of obesity is higher in African Americans than whites, even after adjustment for socioeconomic status (SES). This leads to the hypothesis that differences in genetic background may contribute to racial/ethnic differences in obesity-related traits. We tested this hypothesis by conducting a genome-wide admixture mapping scan using 1,350 ancestry-informative single-nucleotide polymorphisms (SNPs) in 3,531 self-identified blacks from the Atherosclerosis Risk in Communities (ARIC) study. We used these markers to estimate the overall proportions of European ancestry (PEAs) for each individual and then scanned for the association between PEA and obesity-related traits (both continuous and dichotomous) at each locus. The median (interquartile range) PEA was 0.151 (0.115). PEA was inversely correlated with continuous BMI, weight, and subscapular skinfold thickness, even after adjusting for socioeconomic factors. In contrast, PEA was positively correlated with BMI-adjusted waist circumference. Using admixture mapping on dichotomized traits, we identified a locus on 2p23.3 to be suggestively associated with BMI (locus-specific lod = 4.11) and weight (locus-specific lod = 4.07). After adjusting for global PEA, each additional copy of a European ancestral allele at the 2p23.3 peak was associated with a BMI decrease of approximately 0.92 kg/m(2) (P = 2.9 x 10(-5)). Further mapping in this region on chromosome 2 may be able to uncover causative variants underlying obesity, which may offer insights into the control of energy homeostasis.

DOI10.1038/oby.2009.282
Alternate JournalObesity (Silver Spring)
PubMed ID19696751
PubMed Central IDPMC2866099
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
K01 DK067207 / DK / NIDDK NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
N01HV48195 / HL / NHLBI NIH HHS / United States
N01HG65403 / HG / NHGRI NIH HHS / United States
N01-HV-48195 / HV / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
U01 HG004168 / HG / NHGRI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R21DK073482 / DK / NIDDK NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
K01DK067207 / DK / NIDDK NIH HHS / United States
Z99 HG999999 / / Intramural NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R21 DK073482 / DK / NIDDK NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
U01-HG004168 / HG / NHGRI NIH HHS / United States