Male-pattern baldness (MPB) is the most common cause of hair loss in men. It can be categorized into three types: type 2 (T2), type 3 (T3), and type 4 (T4), with type 1 (T1) being considered normal. Although various MPB-associated genetic variants have been suggested, a comprehensive study for linking these variants to gene expression regulation has not been performed to the best of our knowledge. In this study, we prioritized MPB-related tissue panels using tissue-specific enrichment analysis and utilized single-tissue panels from genotype-tissue expression version 8, as well as cross-tissue panels from context-specific genetics. Through a transcriptome-wide association study and colocalization analysis, we identified 52, 75, and 144 MPB associations for T2, T3, and T4, respectively. To assess the causality of MPB genes, we performed a conditional and joint analysis, which revealed 10, 11, and 54 putative causality genes for T2, T3, and T4, respectively. Finally, we conducted drug repositioning and identified potential drug candidates that are connected to MPB-associated genes. Overall, through an integrative analysis of gene expression and genotype data, we have identified robust MPB susceptibility genes that may help uncover the underlying molecular mechanisms and the novel drug candidates that may alleviate MPB.

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通过全转录组关联研究优先考虑男性型秃发预后的易感基因

男性型秃发（MPB）是男性脱发的最常见原因。它可以分为三种类型：2型（T2）、3型（T3）和4型（T4），其中1型（T1）被认为是正常的。尽管已经提出了各种与 MPB 相关的遗传变异，但据我们所知，尚未进行将这些变异与基因表达调控联系起来的全面研究。在这项研究中，我们使用组织特异性富集分析优先考虑 MPB 相关的组织面板，并利用基因型组织表达版本 8 的单组织面板，以及来自特定背景遗传学的跨组织面板。通过全转录组关联研究和共定位分析，我们分别鉴定了 T2、T3 和 T4 的 52、75 和 144 个 MPB 关联。为了评估 MPB 基因的因果关系，我们进行了条件联合分析，结果分别揭示了 T2、T3 和 T4 的 10、11 和 54 个假定因果关系基因。最后，我们进行了药物重新定位并确定了与 MPB 相关基因相关的潜在候选药物。总的来说，通过对基因表达和基因型数据的综合分析，我们已经确定了强大的 MPB 易感基因，这可能有助于揭示潜在的分子机制和可能缓解 MPB 的新候选药物。