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Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X.


ABSTRACT: The prevalence of obesity (body mass index (BMI) > or =30 kg/m(2)) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (rho = -0.042, P = 1.6x10(-7)). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = -3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = -4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI.

SUBMITTER: Cheng CY 

PROVIDER: S-EPMC2679192 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X.

Cheng Ching-Yu CY   Kao W H Linda WH   Patterson Nick N   Tandon Arti A   Haiman Christopher A CA   Harris Tamara B TB   Xing Chao C   John Esther M EM   Ambrosone Christine B CB   Brancati Frederick L FL   Coresh Josef J   Press Michael F MF   Parekh Rulan S RS   Klag Michael J MJ   Meoni Lucy A LA   Hsueh Wen-Chi WC   Fejerman Laura L   Pawlikowska Ludmila L   Freedman Matthew L ML   Jandorf Lina H LH   Bandera Elisa V EV   Ciupak Gregory L GL   Nalls Michael A MA   Akylbekova Ermeg L EL   Orwoll Eric S ES   Leak Tennille S TS   Miljkovic Iva I   Li Rongling R   Ursin Giske G   Bernstein Leslie L   Ardlie Kristin K   Taylor Herman A HA   Boerwinckle Eric E   Zmuda Joseph M JM   Henderson Brian E BE   Wilson James G JG   Reich David D  

PLoS genetics 20090522 5


The prevalence of obesity (body mass index (BMI) > or =30 kg/m(2)) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adju  ...[more]

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