Cross trait analysis reveals shared genetic architecture of eight common female reproductive disorders

Female reproductive disorders widely affect women of reproductive age, yet their shared genetic basis remains incompletely understood, limiting insight into the biological mechanisms linking these conditions. Here, we analyse genetic data from eight common female reproductive disorders to define their shared genetic architecture, primarily through a latent common factor genome wide association study and complemented by a multivariate genome wide association study. We integrate functional annotation to characterise associated loci and use fine mapping to prioritise putative causal variants. We also integrate Multi marker Analysis of GenoMic Annotation and transcriptome wide association analysis to identify candidate susceptibility genes. In addition, we systematically evaluate associations between female reproductive disorders and a broad range of phenotypes and examine their relationships with metabolites, inflammatory mediators, and plasma proteins. Finally, by integrating tissue specific expression, cell type enrichment, and functional genomic annotation, we investigate prioritised susceptibility loci and their putative regulatory elements.女性生殖系统疾病（female reproductive disorders）广泛累及育龄女性，但其共同遗传基础仍未完全阐明，这限制了学界对这类疾病关联背后生物学机制的深入认知。本研究针对8种常见女性生殖系统疾病的遗传数据展开分析，以明确其共同遗传结构，主要采用潜变量公共因子全基因组关联研究（latent common factor genome wide association study）方法，并辅以多变量全基因组关联研究（multivariate genome wide association study）。本研究整合功能注释（functional annotation）以表征关联位点（associated loci），并通过精细定位（fine mapping）筛选潜在致病变异（putative causal variants）。本研究还整合基因组注释多标记分析（Multi marker Analysis of GenoMic Annotation）与转录组全基因组关联分析（transcriptome wide association analysis），以识别候选易感基因（susceptibility genes）。此外，本研究系统评估了女性生殖系统疾病与多种表型之间的关联，并分析了其与代谢物（metabolites）、炎症介质（inflammatory mediators）及血浆蛋白（plasma proteins）的相关性。最后，本研究整合组织特异性表达（tissue specific expression）、细胞类型富集（cell type enrichment）及功能基因组注释（functional genomic annotation）数据，对筛选得到的易感位点（susceptibility loci）及其潜在调控元件（putative regulatory elements）展开深入探究。