MYH9 is associated with nondiabetic end-stage renal disease in African Americans

被引：516

作者：

Kao, W. H. Linda ^{[1
,2
,3
]}

Klag, Michael J. ^{[1
,2
,3
]}

Meoni, Lucy A. ^{[2
,3
,4
,5
]}

Reich, David ^{[6
,7
,8
]}

Berthier-Schaad, Yvette ^{[1
]}

Li, Man ^{[1
]}

Coresh, Josef ^{[1
,3
,4
,5
]}

Patterson, Nick ^{[7
,8
]}

Tandon, Arti ^{[6
,7
,8
]}

Powe, Neil R. ^{[1
,2
,3
]}

Fink, Nancy E. ^{[1
,2
,3
]}

Sadler, John H. ^{[9
]}

Weir, Matthew R. ^{[9
]}

Abboud, Hanna E. ^{[10
]}

Adler, Sharon G. ^{[11
]}

Divers, Jasmin ^{[12
]}

Iyengar, Sudha K. ^{[13
]}

Freedman, Barry I. ^{[12
]}

Kimmel, Paul L. ^{[14
]}

Knowler, William C. ^{[15
]}

Kohn, Orly F. ^{[16
]}

Kramp, Kristopher ^{[13
]}

Leehey, David J. ^{[17
]}

Nicholas, Susanne B. ^{[18
]}

Pahl, Madeleine V. ^{[19
]}

Schelling, Jeffrey R. ^{[20
]}

Sedor, John R. ^{[20
,21
]}

Thornley-Brown, Denyse ^{[22
]}

Winkler, Cheryl A. ^{[23
]}

Smith, Michael W. ^{[23
]}

Parekh, Rulan S. ^{[1
,2
,3
,24
]}

机构：

[1] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Dept Med, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA

[4] Johns Hopkins Univ, Dept Biostat, Sch Med, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA

[6] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[7] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA

[8] MIT, Cambridge, MA 02142 USA

[9] Univ Maryland, Dept Med, Baltimore, MD 21201 USA

[10] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA

[11] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Med, Los Angeles, CA 90502 USA

[12] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27157 USA

[13] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44109 USA

[14] NIDDK, NIH, Bethesda, MD 20892 USA

[15] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA

[16] Loyola Univ, Dept Med, Chicago, IL 60153 USA

[17] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[18] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA

[19] Univ Calif Irvine, Dept Med, Irvine, CA 92868 USA

[20] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44109 USA

[21] Case Western Reserve Univ, Sch Med, Dept Biophysiol & Biophys, Cleveland, OH 44109 USA

[22] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[23] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA

[24] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 10期

基金：

美国国家卫生研究院; 美国医疗保健研究与质量局;

关键词：

D O I：

10.1038/ng.232

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.

引用

页码：1185 / 1192

页数：8

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