孟德尔随机化
肾病
共域化
生物
计算生物学
蛋白质组
疾病
医学
免疫学
生物信息学
遗传学
基因
内科学
糖尿病
遗传变异
细胞生物学
内分泌学
基因型
作者
Chengzhou Tang,Pei Chen,Luo Xu,Jicheng Lv,Sufang Shi,Xu‐jie Zhou,Lijun Liu,Hong Zhang
出处
期刊:Journal of The American Society of Nephrology
日期:2024-04-30
标识
DOI:10.1681/asn.0000000000000379
摘要
Background: The therapeutic options for IgA nephropathy are rapidly evolving, but early diagnosis and targeted treatment remain challenging. We aimed to identify circulating plasma proteins associated with IgA nephropathy by proteome-wide mendelian randomization studies across multiple ancestry populations. Methods: In this study, we applied Mendelian randomization and colocalization analyses to estimate the putative causal effects of 2615 proteins on IgA nephropathy in Europeans and 235 proteins in East Asians. Following two-stage network Mendelian randomization, multi-trait colocalization analysis and protein-altering variant annotation were performed to strengthen the reliability of the results. A protein-protein interaction network was constructed to investigate the interactions between the identified proteins and the targets of existing medications. Results: Putative causal effects of 184 and 13 protein-disease pairs in European and East Asian ancestries were identified, respectively. Two protein-disease pairs showed shared causal effects across them (CFHR1 and FCRL2). Supported by the evidence from colocalization analysis, potential therapeutic targets were prioritized and four drug-repurposing opportunities were suggested. The protein-protein interaction network further provided strong evidence for existing medications and pathways that are known to be therapeutically important. Conclusions: Our study identified a number of circulating proteins associated with IgA nephropathy and prioritized several potential drug targets that require further investigation.
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