Admixture mapping of obesity-related traits in african americans: The atherosclerosis risk in communities (ARIC) study

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, W. H.Linda Kao

Research output: Contribution to journalArticle

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 ∼0.92kg/m 2 (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.

Original languageEnglish (US)
Pages (from-to)563-572
Number of pages10
JournalObesity
Volume18
Issue number3
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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    Cheng, C. Y., Reich, D., Coresh, J., Boerwinkle, E., Patterson, N., Li, M., North, K. E., Tandon, A., Bailey-Wilson, J. E., Wilson, J. G., & Kao, W. H. L. (2010). Admixture mapping of obesity-related traits in african americans: The atherosclerosis risk in communities (ARIC) study. Obesity, 18(3), 563-572. https://doi.org/10.1038/oby.2009.282