Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

被引：64

作者：

Cheng, Ching-Yu ^{[1
,2
,3
]}

Kao, W. H. Linda ^{[1
,4
]}

Patterson, Nick ^{[5
]}

Tandon, Arti ^{[5
,6
]}

Haiman, Christopher A. ^{[7
]}

Harris, Tamara B. ^{[8
]}

Xing, Chao ^{[9
,10
,11
]}

John, Esther M. ^{[12
,13
,14
]}

Ambrosone, Christine B. ^{[15
]}

Brancati, Frederick L. ^{[1
,4
]}

Coresh, Josef ^{[1
,4
]}

Press, Michael F. ^{[16
]}

Parekh, Rulan S. ^{[17
,18
]}

Klag, Michael J. ^{[1
,18
,19
]}

Meoni, Lucy A. ^{[18
,20
]}

Hsueh, Wen-Chi ^{[21
]}

Fejerman, Laura ^{[21
,22
,23
]}

Pawlikowska, Ludmila ^{[22
,24
]}

Freedman, Matthew L. ^{[5
,25
]}

Jandorf, Lina H. ^{[26
]}

Bandera, Elisa V. ^{[27
]}

Ciupak, Gregory L. ^{[15
]}

Nalls, Michael A. ^{[8
,28
]}

Akylbekova, Ermeg L. ^{[29
]}

Orwoll, Eric S. ^{[30
]}

Leak, Tennille S. ^{[31
]}

Miljkovic, Iva ^{[31
]}

Li, Rongling ^{[32
]}

Ursin, Giske ^{[7
,33
]}

Bernstein, Leslie ^{[7
,34
]}

Ardlie, Kristin ^{[5
,35
]}

Taylor, Herman A. ^{[36
,37
,38
]}

Boerwinckle, Eric ^{[39
]}

Zmuda, Joseph M. ^{[31
]}

Henderson, Brian E. ^{[7
]}

Wilson, James G. ^{[38
,40
]}

Reich, David ^{[5
,6
]}

机构：

[1] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

[2] Natl Yang Ming Univ, Sch Med, Dept Ophthalmol, Taipei 112, Taiwan

[3] Taipei Vet Gen Hosp, Taipei, Taiwan

[4] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA

[5] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA

[6] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[7] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[8] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA

[9] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA

[10] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA

[11] Univ Texas SW Med Ctr Dallas, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA

[12] No Calif Canc Ctr, Fremont, CA USA

[13] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA

[14] Stanford Canc Ctr, Stanford, CA USA

[15] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[16] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA

[17] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA

[18] Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA

[19] Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA

[20] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA

[21] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

[22] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[23] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[24] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA

[25] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[26] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA

[27] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA

[28] NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA

[29] Jackson State Univ, Jackson Heart Study Anal Grp, Jackson, MS USA

[30] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA

[31] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA

[32] Univ Tennessee, Dept Prevent Med, Div Biostat & Epidemiol, Memphis, TN USA

[33] Univ Oslo, Dept Nutr, Oslo, Norway

[34] City Hope Natl Med Ctr, Dept Canc Etiol, Div Populat Sci, Duarte, CA 91010 USA

[35] Genom Collaborat, Cambridge, MA USA

[36] Jackson State Univ, Jackson, MS USA

[37] Tougaloo Coll, Tougaloo, MS USA

[38] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA

[39] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA

[40] GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA

来源：

PLOS GENETICS | 2009年 / 5卷 / 05期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE SCAN; FTO GENE; CART GENE; UNITED-STATES; FAT MASS; ASSOCIATION; DISEASE; VARIANTS; RISK; REVEALS;

D O I：

10.1371/journal.pgen.1000490

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The prevalence of obesity (body mass index (BMI) >= 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 = 1.6 x 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 = -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.

引用

页数：10

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