Genome-Wide Analysis Of 64 Male Reproductive Phenotypes Reveals Novel Loci And Shared Biological Pathways

Male reproductive disorders affect millions of men worldwide, yet their genetic basis remains poorly understood. Conditions such as infertility, erectile dysfunction, prostate disorders and hormonal abnormalities are common, interconnected and often diagnosed late, underscoring the need for broader biological insight. Using genetic data from over 530,000 men across the Estonian Biobank, FinnGen, and UK Biobank, we analysed 64 male reproductive phenotypes. We identified 143 lead variants associated with these conditions, including 47 not previously linked to male reproductive traits, and detected the first genome-wide signals for 3 understudied disorders. Twelve lead variants showed at least 1.5-fold enrichment in the Finnish and Estonian populations, indicating population-specific effects and utility of isolated cohorts for variant discovery. We also highlighted 328 candidate genes and mapped shared biological pathways across prostate, testicular, penile and hormonal traits. These findings expand knowledge of male reproductive biology and offer entry points for improved diagnosis and risk prediction.