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...