Genetic overlap and causal inferences between kidney function and cerebrovascular disease

Objective: Leveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes. Methods: We used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease (CKD) diagnosis, estimated glomerular filtration rate (eGFR), and Urinary Albumin-to-Creatinine Ratio (UACR)), and of cerebrovascular disease phenotypes: ischemic stroke and its subtypes, intracerebral hemorrhage (ICH), white matter hyperintensities (WMH) on brain MRI. We (i) tested the genetic overlap between them with polygenic risk scores (PRS), (ii) searched for common pleiotropic loci with pairwise GWAS analyses, and (iii) explored causal associations by employing two-sample Mendelian Randomization (MR). Results: A PRS for lower eGFR was associated with higher large-artery stroke (LAS) risk (p=1x10-4). Multiple pleiotropic loci were identified between kidn...研究目标：依托大规模遗传数据，旨在鉴定肾功能受损与脑血管疾病表型之间共有的致病机制及因果关联。 研究方法：本研究采用了肾功能性状（慢性肾病（CKD）诊断、估算肾小球滤过率（eGFR）、尿白蛋白肌酐比（UACR））以及脑血管疾病表型（缺血性卒中及其亚型、脑出血（ICH）、脑MRI所示脑白质高信号（WMH））的全基因组关联研究（GWAS）汇总统计数据。具体开展了三项分析：(i) 利用多基因风险评分（PRS）检验二者间的遗传重叠情况；(ii) 通过成对全基因组关联分析（GWAS）寻找共同的多效性基因座；(iii) 采用双样本孟德尔随机化（MR）方法探究因果关联。 研究结果：低eGFR的多基因风险评分与更高的大动脉卒中（LAS）发病风险相关（p=1×10^-4）。在肾脏与……之间鉴定出多个多效性基因座