Identifying causal genes for stroke via integrating the proteome and transcriptome from brain and blood

• DOI: 10.1186/s12967-022-03377-9
• Publication Date: 2022-04-21T09:06:04Z
• Authors: Bang-Sheng Wu; Shu-Fen Chen; Shu-Yi Huang; Ya-Nan Ou; Yue-Ting Deng; Shi-Dong Chen; Qiang Dong; Jin-Tai Yu
• Keywords: Mendelian Randomization; Genome-wide Association Study; Stroke; Genetic Association; Proteome; Pathogenesis

Abstract Background Genome-wide association studies (GWAS) have revealed numerous loci associated with stroke. However, the underlying mechanisms at these in pathogenesis of stroke and effective drug targets are elusive. Therefore, we aimed to identify causal genes its subtypes. Methods Utilizing multidimensional high-throughput data generated, integrated proteome-wide study (PWAS), transcriptome-wide (TWAS), Mendelian randomization (MR), Bayesian colocalization analysis prioritize that contribute subtypes risk via affecting their expression protein abundance brain blood. Results Our integrative ICA1L was small-vessel (SVS), according robust evidence both transcriptional levels based on brain-derived data. We also identified NBEAL1 causally related SVS cis-regulated level. In blood, 5 ( MMP12 , SCARF1 ABO F11 CKAP2 ) had relationships Conclusions Together, using an deal data, prioritized SVS, which offered hints for future biological therapeutic studies.