African Ancestry and Its Correlation to Type 2 Diabetes in African Americans: A Genetic Admixture Analysis in Three US Population Cohorts

被引：67

作者：

Cheng, Ching-Yu ^{[1
,4
,5
,6
,7
]}

Reich, David ^{[8
,11
]}

Haiman, Christopher A. ^{[10
]}

Tandon, Arti ^{[8
,11
]}

Patterson, Nick ^{[11
]}

Elizabeth, Selvin ^{[1
,2
]}

Akylbekova, Ermeg L. ^{[12
]}

Brancati, Frederick L. ^{[1
,2
,3
]}

Coresh, Josef ^{[1
,2
]}

Boerwinkle, Eric ^{[13
]}

Altshuler, David ^{[9
,11
,14
,15
]}

Taylor, Herman A. ^{[17
]}

Henderson, Brian E. ^{[10
]}

Wilson, James G. ^{[16
]}

Kao, W. H. Linda ^{[1
,3
]}

机构：

[1] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA

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

[3] Johns Hopkins Univ, Dept Med, Baltimore, MD USA

[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore

[5] Natl Univ Singapore, Yong Loo Lin Sch Med, Saw Swee Hock Sch Publ Hlth, Singapore 117595, Singapore

[6] Duke NUS Grad Med Sch, Singapore, Singapore

[7] Singapore Eye Res Inst, Singapore, Singapore

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

[9] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[10] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA

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

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

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

[14] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[15] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA

[16] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA

[17] Jackson State Univ, Tougaloo Coll, Jackson, MS USA

来源：

PLOS ONE | 2012年 / 7卷 / 03期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; PROSTATE-CANCER RISK; INSULIN-RESISTANCE; ATHEROSCLEROSIS RISK; SOCIOECONOMIC-STATUS; SUSCEPTIBILITY LOCI; DISEASE; SENSITIVITY; SECRETION; VARIANT;

D O I：

10.1371/journal.pone.0032840

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13-1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0) and 13q14.3 (Z score = 4.5, P = 6.6x10(-6)). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes risk.

引用

页数：9

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