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. A cross-trait multivariate genome-wide association study of eight common female reproductive disorders identifies shared risk loci and candidate susceptibility genes, providing insight into their shared genetic basis.