Exome-based genome-wide screening of rare variants associated with the risk of polycystic ovary syndrome.

Purpose: Genetic factors associated with the risk of polycystic ovary syndrome (PCOS) remain largely unknown. Here, we conducted an optimal sequence kernel association test (SKAT-O), an exome-based rare variant association study, to clarify whether rare variants in specific genes contribute to the development of PCOS.

Methods: SKAT-O was performed using exome data of 44 Japanese patients with PCOS and 301 control women. We analyzed frequencies of rare probably damaging variants in the genome.

Results: Rare variants of were more commonly identified in the patient group than in the control group (6/44 vs. 1/301; Bonferroni-corrected -value, 0.028), while the frequencies of variants in other genes were comparable between the two groups. The identified variants were predicted to affect the function, structure, stability, hydrophobicity, and/or the formation of intrinsically disordered regions of the protein. encodes a glutathione transferase that mediates the oxidative stress response and arsenic metabolism. Previously, common variants in and its paralog were associated with the risk of PCOS.

Conclusions: The results indicate that there are no genes whose rare variants account for a large fraction of the etiology of PCOS, although rare damaging variants in may constitute a risk factor in some cases.