Supplementary Material for: Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci

<b><i>Background:</i></b> Serum urea level is a heritable trait, commonly used as a diagnostic marker for kidney function. Genome-wide association studies (GWAS) in East-Asian populations identified a number of genetic loci related to serum urea, however there is a paucity of data for European populations. <b><i>Methods:</i></b> We performed a two-stage meta-analysis of GWASs on serum urea in 13,312 participants, with independent replication in 7,379 participants of European ancestry. <b><i>Results:</i></b> We identified 6 genome-wide significant single nucleotide polymorphisms (SNPs) in or near 6 loci, of which 2 were novel (<i>POU2AF1</i> and <i>ADAMTS9-AS2</i>). Replication of East-Asian and Scottish data provided evidence for an additional 8 loci. SNPs tag regions previously associated with anthropometric traits, serum magnesium, and urinary albumin-to-creatinine ratio, as well as expression quantitative trait loci for genes preferentially expressed in kidney and gastro-intestinal tissues. <b><i>Conclusions:</i></b> Our findings provide insights into the genetic underpinnings of urea metabolism, with potential relevance to kidney function.**<i>背景：</i>** 血清尿素水平属于可遗传性状，常被用作肾脏功能的临床诊断标志物。既往针对东亚人群开展的全基因组关联研究（Genome-wide association studies, GWAS）已鉴定出多个与血清尿素水平相关的遗传基因座，但欧洲人群的相关研究数据仍较为匮乏。 **<i>方法：</i>** 我们对13312名参与者的血清尿素水平开展了两阶段全基因组关联研究荟萃分析，并在7379名欧洲血统参与者中完成了独立重复验证。 **<i>结果：</i>** 我们在6个遗传基因座内部或其邻近区域，鉴定出6个达到全基因组显著性阈值的单核苷酸多态性（single nucleotide polymorphisms, SNPs），其中2个为全新发现的基因座（POU2AF1和ADAMTS9-AS2）。对东亚及苏格兰人群数据的重复验证还额外确认了8个相关基因座。上述SNPs所标记的基因组区域此前已被证实与人体测量性状、血清镁水平、尿白蛋白与肌酐比值相关，同时也是优先在肾脏及胃肠组织中表达的基因的表达数量性状基因座。 **<i>结论：</i>** 本研究结果为尿素代谢的遗传调控机制提供了新的见解，其发现或与肾脏功能存在潜在的临床关联。