Multi-trait genetic analysis identifies novel pleiotropic loci for stroke and hematological traits or risk factors

• Published in: Fundamental research (Beijing) 2024-05
• Main Authors: Jiang, Yue, Song, Yingchao, Li, Yaqi, Tong, Yuhao, Ding, Huanxin, Li, Linzehao, Yang, Ziyue, Meng, Ziang, Guo, Miao, Su, Steven Weidong, Chang, Xiao
• Format: Article
• Language: English
• Subjects: Genome-wide cross-trait analysis; Hypertension; Ischemic stroke; Stroke; Venous thromboembolism
• ISSN: 2667-3258; 2667-3258
• DOI: 10.1016/j.fmre.2024.05.004

Accumulating evidence suggests a correlation between stroke and hematological traits along with their associated risk factors, yet the precise shared genetic basis remains elusive. We collected GWAS summary statistics of stroke and potentially related hematological traits or risk factors from the GWAS Catalog and used LDSC to estimate genetic correlations and heritabilities. For trait pairs with significant correlations, we performed a comprehensive multi-trait GWAS analysis to identify pleiotropic loci shared by stroke and genetically correlated hematological traits or risk factors in both Europeans and East Asians. Our MTAG analysis identified 59 pleiotropic loci associated with both stroke and hypertension in Europeans, along with 17 such loci in East Asians. Among these loci, 33 were previously unknown in Europeans, and six were previously unknown in East Asians, suggesting potential new insights into the genetic basis of these traits. In the MTAG analysis of ischemic stroke and venous thromboembolism, we found six known loci and two novel loci. Notably, the 10q22.1 locus (rs12242391) was identified as an eQTL for the nearby gene TSPAN15 in multiple tissues, including whole blood. Furthermore, the 12q13.13 locus (rs4759076), which had not been reported in association with ischemic stroke or venous thromboembolism previously, exhibited a strong cis-eQTL effect with the nearby gene NFE2, a crucial regulator of megakaryocyte biogenesis and platelet production. Our study provided valuable insights into the shared genetic architecture of stroke and hematological traits or risk factors, highlighting potential avenues for future research and clinical applications. [Display omitted]