Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X.
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.
Cheng
Ching-Yu
CY
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA. cycheng@jhsph.edu
Kao
W H Linda
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Patterson
Nick
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Tandon
Arti
A
Haiman
Christopher A
CA
Harris
Tamara B
TB
Xing
Chao
C
John
Esther M
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Ambrosone
Christine B
CB
Brancati
Frederick L
FL
Coresh
Josef
J
Press
Michael F
MF
Parekh
Rulan S
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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
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Nalls
Michael A
MA
Akylbekova
Ermeg L
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Orwoll
Eric S
ES
Leak
Tennille S
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Miljkovic
Iva
I
Li
Rongling
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Ursin
Giske
G
Bernstein
Leslie
L
Ardlie
Kristin
K
Taylor
Herman A
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Boerwinckle
Eric
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Zmuda
Joseph M
JM
Henderson
Brian E
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Wilson
James G
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Reich
David
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D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014481:United States; D044465:White People / Q000235:genetics