Kao W H Linda, Klag Michael J, Meoni Lucy A, Reich David, Berthier-Schaad Yvette, Li Man, Coresh Josef, Patterson Nick, Tandon Arti, Powe Neil R, Fink Nancy E, Sadler John H, Weir Matthew R, Abboud Hanna E, Adler Sharon G, Divers Jasmin, Iyengar Sudha K, Freedman Barry I, Kimmel Paul L, Knowler William C, Kohn Orly F, Kramp Kristopher, Leehey David J, Nicholas Susanne B, Pahl Madeleine V, Schelling Jeffrey R, Sedor John R, Thornley-Brown Denyse, Winkler Cheryl A, Smith Michael W, Parekh Rulan S
Department of Epidemiology, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Nat Genet. 2008 Oct;40(10):1185-92. doi: 10.1038/ng.232. Epub 2008 Sep 14.
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.
由于终末期肾病（ESRD）在非裔美国人中的发病率比欧裔美国人高四倍，我们推测ESRD的易感等位基因在西非基因库中的频率高于欧洲基因库。我们对1372例ESRD病例和806例对照进行了全基因组混合扫描，发现在22q12染色体上，非洲血统过多与非糖尿病性ESRD之间存在高度显著的关联（lod分数 = 5.70），但与糖尿病性ESRD无关联（lod = 0.47）。与非洲血统相比，欧洲祖先等位基因的每个拷贝赋予的相对风险为0.50（95%置信区间 = 0.39 - 0.63）。编码非肌肉肌球蛋白重链IIA型（MYH9）的基因中的多个常见单核苷酸多态性（等位基因频率范围为0.2至0.6）与非糖尿病性ESRD的风险高两至四倍相关，并且在非裔美国人与欧裔美国人相比中，占观察到的ESRD额外风险的很大一部分。
