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

Ching Yu Cheng, W. H Linda Kao, Nick Patterson, Arti Tandon, Christopher A. Haiman, Tamara B. Harris, Chao Xing, Esther M. John, Christine B. Ambrosone, Frederick L. Brancati, Josef Coresh, Michael F. Press, Rulan S. Parekh, Michael John Klag, Lucy Ann Meoni, Wen Chi Hsueh, Laura Fejerman, Ludmila Pawlikowska, Matthew L. Freedman, Lina H. Jandorf & 17 others Elisa V. Bandera, Gregory L. Ciupak, Michael A. Nalls, Ermeg L. Akylbekova, Eric S. Orwoll, Tennille S. Leak, Iva Miljkovic, Rongling Li, Giske Ursin, Leslie Bernstein, Kristin Ardlie, Herman A. Taylor, Eric Boerwinckle, Joseph M. Zmuda, Brian E. Henderson, James G. Wilson, David Reich

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere1000490
JournalPLoS Genetics
Volume5
Issue number5
DOIs
StatePublished - May 2009

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Chromosomes, Human, Pair 5
obesity
African American
African Americans
body mass
body mass index
chromosome
Body Mass Index
Obesity
chromosomes
ancestry
loci
genome
Genome
X chromosome
Genetic Loci
socioeconomic factors
X Chromosome
epidemiological studies
quantitative analysis

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Cheng, C. Y., Kao, W. H. L., Patterson, N., Tandon, A., Haiman, C. A., Harris, T. B., ... Reich, D. (2009). Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X. PLoS Genetics, 5(5), [e1000490]. https://doi.org/10.1371/journal.pgen.1000490

Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X. / Cheng, Ching Yu; 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 John; Meoni, Lucy Ann; 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.

In: PLoS Genetics, Vol. 5, No. 5, e1000490, 05.2009.

Research output: Contribution to journalArticle

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, I, Li, R, Ursin, G, Bernstein, L, Ardlie, K, Taylor, HA, Boerwinckle, E, Zmuda, JM, Henderson, BE, Wilson, JG & Reich, D 2009, 'Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X', PLoS Genetics, vol. 5, no. 5, e1000490. https://doi.org/10.1371/journal.pgen.1000490
Cheng, Ching Yu ; 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 John ; Meoni, Lucy Ann ; 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. / Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X. In: PLoS Genetics. 2009 ; Vol. 5, No. 5.
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abstract = "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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AU - Harris, Tamara B.

AU - Xing, Chao

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AU - Brancati, Frederick L.

AU - Coresh, Josef

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AU - Leak, Tennille S.

AU - Miljkovic, Iva

AU - Li, Rongling

AU - Ursin, Giske

AU - Bernstein, Leslie

AU - Ardlie, Kristin

AU - Taylor, Herman A.

AU - Boerwinckle, Eric

AU - Zmuda, Joseph M.

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