Mendelian Randomization Analysis Identified Potential Genes Pleiotropically Associated with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with unclear etiology. Some genes may be pleiotropically or potentially causally associated with PCOS. In the present study, the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for PCOS and expression quantitative trait loci (eQTL) data was applied to identify genes that were pleiotropically associated with PCOS. Separate SMR analysis was performed using eQTL data in the ovary and whole blood. Although no genes showed significant pleiotropic association with PCOS after correction for multiple testing, some of the genes exhibited suggestive significance. RPS26 showed the strongest suggestive pleiotropic association with PCOS in both SMR analyses (β[SE]=0.10[0.03], PSMR=1.72×10-4 for ovary; β[SE]=0.11[0.03], PSMR=1.40×10-4 for whole blood). PM20D1 showed the second strongest suggestive pleiotropic association with PCOS in the SMR analysis using eQTL data for the whole blood and was also among the top ten hit genes in the SMR analysis using eQTL data for the ovary. Two other genes, including CTC-457L16.2 and NEIL2, were among the top ten hit genes in both SMR analyses. In conclusion, this study revealed multiple genes that were potentially involved in the pathogenesis of PCOS.