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PMID: 19461885 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

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

PLoS genetics ·Vol. 5 ·No. 5 ·2009-05-00 ·Pages e1000490

Cheng CY, Kao WH, Patterson N, Tandon A, Haiman CA, Harris TB, Xing C, John EM, Ambrosone CB, Brancati FL, Coresh J, Press MF, Parekh RS, Klag MJ, Meoni LA, Hsueh WC, Fejerman L, Pawlikowska L, Freedman ML, Jandorf LH, Bandera EV, Ciupak GL, Nalls MA, Akylbekova EL, Orwoll ES, Leak TS, Miljkovic I, Li R, Ursin G, Bernstein L, Ardlie K, Taylor HA, Boerwinckle E, Zmuda JM, Henderson BE, Wilson JG, Reich D

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.

MeSH Terms
Adult African Americans/genetics Aged Alleles Body Mass Index Chromosome Mapping Chromosomes, Human, Pair 5/genetics Chromosomes, Human, X/genetics Female Gene Frequency Genetic Predisposition to Disease Humans Male Middle Aged Obesity/genetics Polymorphism, Single Nucleotide United States Whites/genetics
Authors & Affiliations
37 authors, click to expand affiliations / ORCID
Cheng Ching-Yu
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA. cycheng@jhsph.edu
Kao W H Linda
Patterson Nick
Tandon Arti
Haiman Christopher A
Harris Tamara B
Xing Chao
John Esther M
Ambrosone Christine B
Brancati Frederick L
Coresh Josef
Press Michael F
Parekh Rulan S
Klag Michael J
Meoni Lucy A
Hsueh Wen-Chi
Fejerman Laura
Pawlikowska Ludmila
Freedman Matthew L
Jandorf Lina H
Bandera Elisa V
Ciupak Gregory L
Nalls Michael A
Akylbekova Ermeg L
Orwoll Eric S
Leak Tennille S
Miljkovic Iva
Li Rongling
Ursin Giske
Bernstein Leslie
Ardlie Kristin
Taylor Herman A
Boerwinckle Eric
Zmuda Joseph M
Henderson Brian E
Wilson James G
Reich David
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000490
Email
cycheng@jhsph.edu
Published
2009-05-00
Epub
2009-00-22
Pages
e1000490
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2679192
Subset
IM
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PubMed source DOI: 10.1371/journal.pgen.1000490 PMC Full Text View journal details
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