scMRdb 发布:细胞类型分辨的复杂性状孟德尔随机化资源库
scMRdb: a comprehensive resource for cell-type-resolved Mendelian randomization of complex traits
scMRdb 是一个面向人类复杂性状与疾病的细胞类型分辨孟德尔随机化资源库,整合了 5206 套欧洲与东亚人群 GWAS 汇总统计和 585 个 sc-eQTL 数据集,覆盖 11 种组织与细胞体系、110 种细胞类型。研究团队用统一流程对所有基因–性状对做 MR 分析并配合 Steiger 方向性检验,对显著关联再做共定位评估,结果按六个置信层级分层,并整合药物靶点注释。
来源:Nucleic Acids Research · doi.org
该资源把单细胞 eQTL 与大规模 GWAS 统一到同一套 MR 流程,便于按细胞类型检索候选因果基因。
Mendelian randomization (MR) is a powerful analytical approach to infer putative causal links between gene expression and human disease, using genetic variants as instrumental variables to mitigate confounding and reverse causation. However, existing MR resources predominantly rely on bulk-tissue expression quantitative trait loci (eQTLs), which mask cell-type-specific transcriptional effects by averaging expression across cellular populations. Furthermore, cell-type-resolved causal evidence from single-cell eQTL (sc-eQTL) MR analyses remains fragmented across individual studies with inconsistent workflows, prohibiting standardized cross-cell-type comparisons. Here we present scMRdb (https://ngdc.cncb.ac.cn/scmrdb), a comprehensive resource for cell-type-resolved MR of human complex traits and diseases. scMRdb harmonizes 5206 genome-wide association study (GWAS) summary statistics of European and East Asian ancestry with 585 sc-eQTL datasets spanning 11 tissues and cell systems, including 110 cell types. A uniform pipeline evaluates all gene–trait pairs via MR followed by Steiger directionality testing. Significant associations are assessed by colocalization, and results are stratified into six confidence tiers with integrated drug–target annotation. scMRdb enables systematic recovery of candidate causal genes supported by cell-type-resolved regulatory evidence that is often diluted or obscured in bulk-tissue analyses. We expect scMRdb to serve as a user-friendly portal for generating cell-type-informed mechanistic hypotheses and prioritizing actionable therapeutic targets for complex human diseases.