Candidate genes for non-diabetic ESRD in African Americans: a genome-wide association study using pooled DNA.
Candidate genes for non-diabetic ESRD in African Americans: a genome-wide association study using pooled DNA.
复制标题
DOI：
10.1007/s00439-010-0842-3
复制
发表时间：
2010-08
期刊：
影响因子：
5.3
通讯作者：
Freedman BI
中科院分区：
文献类型：
--
作者：
Bostrom MA;Lu L;Chou J;Hicks PJ;Xu J;Langefeld CD;Bowden DW;Freedman BI
非裔美国人对非糖尿病（非DM）形式的终末期肾病（ESRD）的易感性增加，大量证据支持遗传贡献。在1,000名非裔美国人中进行了一项使用合并DNA的全基因组关联研究（GWAS），以检测相关基因。使用凝胶电泳和分光光度分析对来自500个非DM ESRD病例和500个非肾病对照的DNA进行定量，并创建50个病例和50个对照DNA样品的池。在Illumina HumanHap 550-Duo BeadChip上一式两份地对DNA池进行基因分型。开发了归一化方法，并将其应用于阵列强度值，以减少阵列间方差。等位基因频率从标准化通道强度计算，并在病例和对照池之间进行比较。三种SNP具有<1.0E-6的p值：rs 4462445（第13章）、rs 4821469（第22章）和rs 8077346（第17章）。标准化后，在464例原始病例和478例对照中单独对得分最高的SNP（n = 65）进行基因分型，并在336例非DM ESRD病例和363例非肾病对照中进行复制。16个SNP与非DM ESRD相关（p < 7.7E-4，Bonferroni校正）。这些SNP中有12个位于MYH 9基因中或附近。合并样本中与非DM ESRD相关的4个非MYH 9 SNP在复制集中不相关。在合并样本中适度相关的五个SNP在复制和/或组合样本中更强相关。这是第一个使用合并DNA在非裔美国人中进行的非DM ESRD GWAS。我们证明了非裔美国人的非糖尿病ESRD与MYH 9之间的强相关性，并确定了其他候选基因座。
African Americans have increased susceptibility to non-diabetic (non-DM) forms of end-stage renal disease (ESRD) and extensive evidence supports a genetic contribution. A genome-wide association study (GWAS) using pooled DNA was performed in 1,000 African Americans to detect associated genes. DNA from 500 non-DM ESRD cases and 500 non-nephropathy controls was quantified using gel electrophoresis and spectrophotometric analysis and pools of 50 case and 50 control DNA samples were created. DNA pools were genotyped in duplicate on the Illumina HumanHap550-Duo BeadChip. Normalization methods were developed and applied to array intensity values to reduce inter-array variance. Allele frequencies were calculated from normalized channel intensities and compared between case and control pools. Three SNPs had p values of <1.0E–6: rs4462445 (ch 13), rs4821469 (ch 22) and rs8077346 (ch 17). After normalization, top scoring SNPs (n = 65) were genotyped individually in 464 of the original cases and 478 of the controls, with replication in 336 non-DM ESRD cases and 363 non-nephropathy controls. Sixteen SNPs were associated with non-DM ESRD (p < 7.7E–4, Bonferroni corrected). Twelve of these SNPs are in or near the MYH9 gene. The four non-MYH9 SNPs that were associated with non-DM ESRD in the pooled samples were not associated in the replication set. Five SNPs that were modestly associated in the pooled samples were more strongly associated in the replication and/or combined samples. This is the first GWAS for non-DM ESRD in African Americans using pooled DNA. We demonstrate strong association between non-DM ESRD in African Americans with MYH9, and have identified additional candidate loci.
登录
查看更多内容
影响因子：
30.8
作者：
Kopp, Jeffrey B.;Smith, Michael W.;Nelson, George W.;Johnson, Randall C.;Freedman, Barry I.;Bowden, Donald W.;Oleksyk, Taras;McKenzie, Louise M.;Kajiyama, Hiroshi;Ahuja, Tejinder S.;Berns, Jeffrey S.;Briggs, William;Cho, Monique E.;Dart, Richard A.;Kimmel, Paul L.;Korbet, Stephen M.;Michel, Donna M.;Mokrzycki, Michele H.;Schelling, Jeffrey R.;Simon, Eric;Trachtman, Howard;Vlahov, David;Winkler, Cheryl A.
通讯作者：
Winkler, Cheryl A.
影响因子：
19.6
作者：
Freedman, Barry I.;Hicks, Pamela J.;Bowden, Donald W.
通讯作者：
Bowden, Donald W.
影响因子：
--
作者：
Appel, Lawrence J.;Wright, Jackson T., Jr.;Agodoa, Lawrence Y.
通讯作者：
Agodoa, Lawrence Y.
影响因子：
5.3
作者：
Keene, Keith L.;Mychaleckyj, Josyf C.;Sale, Michele M.
通讯作者：
Sale, Michele M.
影响因子：
6.1
作者：
Freedman, BI;Bowden, DW;Langefeld, CD
通讯作者：
Langefeld, CD