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