Yarmolinsky J, Relton CL, Lophatananon A, et al. - In up to 25,509 cases and 40,941 controls in the Ovarian Cancer Association Consortium, MR was used to assess the relationship of 12 previously reported risk factors (reproductive, anthropometric, clinical, lifestyle, and molecular factors) with the risk of invasive epithelial ovarian cancer, invasive epithelial ovarian cancer histotypes, and low malignant potential tumors. In MR analysis, only two of 12 formerly reported risk factors (genetic liability to endometriosis and lifetime smoking exposure) were related to invasive epithelial ovarian cancer risk. Eight risk factors were correlated with one or more epithelial ovarian cancer subtypes when analyses were stratified on invasive epithelial ovarian cancer histotypes and low malignant potential tumors. The most powerful relationships recognized were positive correlations of height with clear cell carcinoma and age at natural menopause with endometrioid carcinoma and an inverse relation of genetic liability to polycystic ovary syndrome with endometrioid carcinoma. Thus, this comprehensive examination of possible aetiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a role for a couple of these factors in invasive epithelial ovarian cancer overall and infers different aetiologies across histotypes. For the prevention of epithelial ovarian cancer, the identification of novel risk factors persists to be a significant priority.