Admixture Mapping of Obesity‐related Traits in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study |
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| Authors: | Ching‐Yu Cheng David Reich Josef Coresh Eric Boerwinkle Nick Patterson Man Li Kari E North Arti Tandon Joan E Bailey‐Wilson James G Wilson WH Linda Kao |
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| Institution: | 1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA;2. Inherited Disease Research Branch, National Human Genome Research Institute, Baltimore, Maryland, USA;3. Department of Opthalmology, National Yang Ming University School of Medicine and Taipei Veterans General Hospital, Taipei, Taiwan;4. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA;5. Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, Massachusetts, USA;6. Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA;7. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA;8. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;9. The V.A. Medical Center and the University of Mississippi Medical Center, Jackson, Mississippi, USA |
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| 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 ～0.92 kg/m2 (P = 2.9 × 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. |
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