A genome scan for all-cause end-stage renal disease in African Americans
A genome scan for all-cause end-stage renal disease in African Americans
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DOI：
10.1093/ndt/gfh704
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发表时间：
2005-04-01
影响因子：
6.1
通讯作者：
Langefeld, CD
中科院分区：
文献类型：
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作者：
Freedman, BI;Bowden, DW;Langefeld, CD
背景为了定位终末期肾病（ESRD）常见、复杂病因的易感基因，我们对来自483个非裔美国家庭的1023名慢性肾病患者（946名透析依赖者和77名晚期慢性肾衰竭患者）进行了全基因组扫描。研究样本包括563对受终末期肾病影响的兄弟姐妹，患有糖尿病、慢性肾小球疾病或高血压引起的肾病。采用多点非参数连锁（NPL）分析方法。NPL回归提供了与D13S796附近的13q33.3 [比值对数（LOD）=1.72]、D9S1826附近的9q34.3（LOD=1.22）、D4S2639附近的4p15.32（LOD = 1.11）和D1S1589附近的1q25.1（LOD=1.01）连锁的适度证据。使用NPL回归分析调整其他位点的连锁证据，提供了与4p15.32，9q34.3和13q33.3连锁的证据。NPL回归交互作用和有序子集分析（OSA）表明，与ESRD相关的证据随着13q33.3的体重指数（BMI）的升高而显著增加（在61%的BMI最高的家庭中LOD=4.94）。另外，OSA分析表明，在13%的最早发病年龄的家族（2q32.1处的LOD=3.05）和16%的最晚发病年龄的家族（10q26.3处的LOD=2.47）中，ESRD发病的连锁显著改善。多点单位点连锁分析提供了适度的证据，连锁的所有原因ESRD在非洲裔美国人13q33.3，和NPL回归和OSA表明，在该地区的连锁证据显着增加肥胖家庭。该区域，以及9q34.3，4p15.32和1q25.1，应优先考虑在非洲裔美国人中寻找有助于ESRD易感性的基因座。
Background. In an attempt to map the genes predisposing to the common, complex aetiologies of end-stage renal disease (ESRD), we performed a genome-wide scan in 1023 individuals with chronic kidney disease (946 dialysis dependent and 77 with advanced chronic renal failure) from 483 African American families.Methods. The study sample comprised 563 ESRD affected sibling pairs, with nephropathy attributed to diabetes mellitus, chronic glomerular disease or hypertension. Multipoint non-parametric linkage (NPL) analysis methods were employed.Results. NPL regression provided modest evidence of linkage to 13q33.3 near D13S796 [log of the odds (LOD)=1.72], 9q34.3 near D9S1826 (LOD=1.22), 4p15.32 near D4S2639 (LOD = 1.11) and 1q25.1 near D1S1589 (LOD=1.01). Adjusting for the evidence of linkage at the other loci using NPL regression analysis provided evidence for linkage to 4p15.32, 9q34.3 and 13q33.3. NPL regression interaction and ordered subset analysis (OSA) suggested that the evidence for linkage to ESRD significantly increased with higher body mass index (BMI) at 13q33.3 (LOD=4.94 in 61% of families with the highest BMI). Additionally, OSA suggested that linkage significantly improved in the 13% of families with earliest age at ESRD onset (LOD=3.05 at 2q32.1) and in the 16% of families with latest age at ESRD onset (LOD=2.47 at 10q26.3).Conclusions. Multipoint single-locus linkage analysis provided modest evidence of linkage to all-cause ESRD in African Americans on 13q33.3, and NPL regression and OSA suggested that evidence for linkage in this region markedly increased in obese families. This region, as well as 9q34.3, 4p15.32 and 1q25.1, should receive priority in the search for loci contributing to ESRD susceptibility in African Americans.