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

Cheng, CY and Kao, WHL and Patterson, N and Tandon, A and Haiman, CA and Harris, TB and Xing, C and John, EM and Ambrosone, CB and Brancati, FL and Coresh, J and Press, MF and Parekh, RS and Klag, MJ and Meoni, LA and Hsueh, WC and Fejerman, L and Pawlikowska, L and Freedman, ML and Jandorf, LH and Bandera, EV and Ciupak, GL and Nalls, MA and Akylbekova, EL and Orwoll, ES and Leak, TS and Miljkovic, I and Li, R and Ursin, G and Bernstein, L and Ardlie, K and Taylor, HA and Boerwinckle, E and Zmuda, JM and Henderson, BE and Wilson, JG and Reich, D (2009) Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X. PLoS Genetics, 5 (5). ISSN 1553-7390

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The prevalence of obesity (body mass index (BMI) $30 kg/m2) 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 (ρ = -0.042, P = 1.6×10 -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 =23.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z =24.62). 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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Cheng, CY
Kao, WHL
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, IMiljkovicI@edc.pitt.eduIVM1
Li, R
Ursin, G
Bernstein, L
Ardlie, K
Taylor, HA
Boerwinckle, E
Zmuda, JMZmudaJ@edc.pitt.eduEPIDJMZ
Henderson, BE
Wilson, JG
Reich, D
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 May 2009
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 5
Number: 5
DOI or Unique Handle: 10.1371/journal.pgen.1000490
Schools and Programs: School of Public Health > Epidemiology
Refereed: Yes
ISSN: 1553-7390
PubMed Central ID: PMC2679192
PubMed ID: 19461885
Date Deposited: 25 Jul 2012 14:13
Last Modified: 22 Jun 2021 15:55


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