Evidence to shared genetic correlation of ischemic stroke and intracerebral hemorrhage and cardiovascular related traits

作者：Wei He, Jiajia Shi, Yiming Qian, Tao Fan, Xuehong Cai, Haochang Li, Peng Huang, Qin Shi · 发表于：PLoS ONE · 年份：2025 · DOI：10.1371/journal.pone.0320479 · 被引用次数：1 · 研究领域：Genetic Associations and Epidemiology、Genomics and Rare Diseases、Bioinformatics and Genomic Networks

BACKGROUND: Previous studies have demonstrated the genetic basis of stroke and also revealed their genetic correlation with some cardiovascular related diseases or traits at the entire genome, which, however, would not give the answer which regions may mainly account for the genetic overlap. This study aims to identify specific genetic loci that contribute to the shared genetic basis between ischemic stroke subtypes and common cardiovascular traits. METHODS: We used Local Analysis of [co]Variant Annotation (LAVA), a recent developed local genetic correlation method, to perform a system local genetic correlation analysis on GWAS summary data of two major subtypes of stroke, including any ischemic stroke (AIS) and intracerebral hemorrhage (ICH), and ten common cardiovascular related diseases or traits (CRTs). We further used colocalization analysis to explore potential shared causal genes in loci with significant local genetic correlation. In addition, we also performed Transcriptome-wide association (TWAS) analysis and fine-mapping for each phenotype to functionally annotate significant loci. RESULTS: LAVA analysis identified a total of 3 significant local genetic correlations (Bonferroni-adjusted P < 0.05) across 3 chromosomes between AIS and systolic blood pressure (SBP), AIS and hypertension (HT), and ICH and body mass index (BMI), among which locus 7.24 explicated to harbor a shared causal variant for AIS and SBP. TWIST1 in locus 7.24 was defined to be nominally associated...