https://www.selleckchem.com/products/brensocatib.html stroke and cognitive impairment. The purpose of this study was to replicate the top loci associated with white matter hyperintensity (WMH) phenotypes identified by large genome-wide association studies and the loci identified from the previous candidate gene studies. A total of 946 Geisinger MyCode patients with acute ischemic stroke with validated European ancestry and magnetic resonance imaging data were included in this study. Log-transformed WMH volume, as a quantitative trait, was calculated by a fully automated quantification process. The genome-wide association studies was carried out by a linear mixed regression model (GEMMA). A candidate-single nucleotide polymorphism analysis by including known single nucleotide polymorphisms, reported from a meta-analysis and several large GWAS for WMH, was conducted in all cases and binary converted extreme cases. No genome-wide significantly associated variants were identified. In a candidate-single nucleotide polymorphism study, rs9515201 ( ) and rs3744028 ( ), 2 known genetic loci, showed nominal or trend of association with the WMH volume (β=0.13 and =0.001 for rs9515201; β=0.094 and =0.094 for rs3744028), and replicated in a subset of extreme cases versus controls (odds ratio=1.78, =7.74×10 for rs9515201; odds ratio=1.53, =0.047 for rs3744028, respectively). MTHFR677 cytosine/thymine (rs1801133) also showed an association with the binary WMH with odds ratio=1.47 for T allele ( =0.019). Replication of COL4A1/2 associated with WMH reassures that the genetic risk factors for monogenic and polygenic ischemic stroke are shared at gene level. Replication of COL4A1/2 associated with WMH reassures that the genetic risk factors for monogenic and polygenic ischemic stroke are shared at gene level. Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association be