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 J. Klag; Lucy A. Meoni; Wen Chi Hsueh; Laura Fejerman; Ludmila Pawlikowska; Matthew L. Freedman; Lina H. Jandorf; 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

doi:10.1371/journal.pgen.1000490

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 J. Klag, Lucy A. Meoni, Wen Chi Hsueh, Laura Fejerman, Ludmila Pawlikowska, Matthew L. Freedman, Lina H. JandorfElisa 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

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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.

Original language	English (US)
Article number	e1000490
Journal	PLoS genetics
Volume	5
Issue number	5
DOIs	https://doi.org/10.1371/journal.pgen.1000490
State	Published - May 2009

ASJC Scopus subject areas

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

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Cheng, C. Y., Kao, W. H. L., Patterson, N., Tandon, A., Haiman, C. A., Harris, T. B., Xing, C., John, E. M., Ambrosone, C. B., Brancati, F. L., Coresh, J., Press, M. F., Parekh, R. S., Klag, M. J., Meoni, L. A., Hsueh, W. C., Fejerman, L., Pawlikowska, L., Freedman, M. L., ... Reich, D. (2009). Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X. PLoS genetics, 5(5), Article e1000490. https://doi.org/10.1371/journal.pgen.1000490

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

@article{708b5d4006084010b918caf8fc719c5e,

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) $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.",

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

year = "2009",

month = may,

doi = "10.1371/journal.pgen.1000490",

language = "English (US)",

volume = "5",

journal = "PLoS genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

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T1 - Admixture mapping of 15,280 African Americans identifies obesity susceptibility loci on chromosomes 5 and X

AU - Cheng, Ching Yu

AU - Kao, W. H Linda

AU - Patterson, Nick

AU - Tandon, Arti

AU - Haiman, Christopher A.

AU - Harris, Tamara B.

AU - Xing, Chao

AU - John, Esther M.

AU - Ambrosone, Christine B.

AU - Brancati, Frederick L.

AU - Coresh, Josef

AU - Press, Michael F.

AU - Parekh, Rulan S.

AU - Klag, Michael J.

AU - Meoni, Lucy A.

AU - Hsueh, Wen Chi

AU - Fejerman, Laura

AU - Pawlikowska, Ludmila

AU - Freedman, Matthew L.

AU - Jandorf, Lina H.

AU - Bandera, Elisa V.

AU - Ciupak, Gregory L.

AU - Nalls, Michael A.

AU - Akylbekova, Ermeg L.

AU - Orwoll, Eric S.

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.

AU - Henderson, Brian E.

AU - Wilson, James G.

AU - Reich, David

PY - 2009/5

Y1 - 2009/5

N2 - 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.

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

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