Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
Nat Genet. 2010 May;42(5):376-84. doi: 10.1038/ng.568. Epub 2010 Apr 11.
Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
慢性肾脏病(CKD)是一个重大的公共卫生问题,最近的遗传研究已经确定了常见的 CKD 易感性变异。CKDGen 联盟对 20 项主要基于人群的研究中 67093 名欧洲血统个体的全基因组关联数据进行了荟萃分析,以确定新的易感性基因座,用于估计肾功能降低的血清肌酐(eGFRcrea)、血清胱抑素 c(eGFRcys)和 CKD(eGFRcrea<60ml/min/1.73m2;n=5807 例 CKD(病例))。对 23 个新的全基因组显著位点(P<5x10(-8))在 22982 个复制样本中的随访确定了 13 个新的影响肾功能和 CKD 的位点(在 LASS2、GCKR、ALMS1、TFDP2、DAB2、SLC34A1、VEGFA、PRKAG2、PIP5K1B、ATXN2、DACH1、UBE2Q2 和 SLC7A9 中或附近)和 7 个疑似影响肌酐产生和分泌的位点(CPS1、SLC22A2、TMEM60、WDR37、SLC6A13、WDR72 和 BCAS3)。这些结果通过鉴定潜在影响肾脏发生、足细胞功能、血管生成、溶质转运和肾脏代谢功能的基因座,进一步了解了肾脏功能的生物学机制。