Summary statistics for "Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis"

Chronic kidney disease (CKD) is a growing health burden currently affecting 10–15% of adults worldwide. Estimated glomerular filtration rate (eGFR) as a marker of kidney function is commonly used to diagnose CKD. We analyze eGFR data from the Nord-Trøndelag Health Study and Michigan Genomics Initiative and perform a GWAS meta-analysis with public summary statistics, more than doubling the sample size of previous meta-analyses. We identify 147 loci (53 novel) associated with eGFR, including genes involved in transcriptional regulation, kidney development, cellular signaling, metabolism, and solute transport. Additionally, sex-stratified analysis identifies one locus with more significant effects in women than men. Using genetic risk scores constructed from these eGFR meta-analysis results, we show that associated variants are generally predictive of CKD with only modest improvements in detection compared with other known clinical risk factors. Collectively, these results yield additional insight into the genetic factors underlying kidney function and progression to CKD.

慢性肾病（CKD）已成为日益沉重的公共卫生负担，目前全球约有10-15%的成年人受到影响。作为肾脏功能的标志物，估算肾小球滤过率（eGFR）常被用于CKD的诊断。我们分析了来自挪威特伦德拉格健康研究和密歇根基因组计划中的eGFR数据，并进行了基于公共汇总统计数据的GWAS荟萃分析，将样本量较之前的荟萃分析翻倍。我们鉴定出与eGFR相关的147个位点（其中53个为新型），包括参与转录调控、肾脏发育、细胞信号传导、代谢和溶质转运的基因。此外，性别分层分析还发现，有一个位点的效应在女性中比男性更为显著。通过构建自这些eGFR荟萃分析结果的遗传风险评分，我们展示出相关变异通常可以预测CKD，与已知其他临床风险因素相比，其在检测方面的改进仅为适度。综合而言，这些结果为揭示肾脏功能及其向CKD进展背后的遗传因素提供了额外的见解。