A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers

Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers, nor the shared genetic influences underlying these conditions. We performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture between COVID-19 (infection, hospitalization, and critical illness) with three female-specific cancers (breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC)). We identified significant genome-wide genetic correlations with EC for both hospitalization ([Formula: see text] = 0.19, p = 0.01) and critical illness ([Formula: see text] = 0.29, p = 3.00 × 10(−4)). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (OR(IVW) = 1.09, p = 0.04) and critical illness (OR(IVW) = 1.06, p = 0.04) with EC risk, none withstanding multiple correction. Cross-trait meta-analysis identified 20 SNPs shared between COVID-19 with BC, 15 with EOC, and 5 with EC; and transcriptome-wide association studies revealed multiple shared genes. Findings support intrinsic links underlying these complex traits, highlighting shared mechanisms rather than causal associations.