Abstract
The etiology of polycystic ovary syndrome (PCOS) has been difficult to determine because
its features are heterogeneous, and its origin may also be heterogeneous. Twin studies
suggest that its etiology is strongly heritable and genetic approaches are rapidly
uncovering new regions of the genome that appear to confer risk for PCOS. Recent genome-wide
association studies in Han Chinese women with PCOS demonstrate 11 genetic loci that
are associated with PCOS. The variants identified are in regions that contain genes
important for gonadotropin action, genes that are associated with risk for type 2
diabetes, and other genes in which the relationship to PCOS is not yet clear. Replication
studies have demonstrated that variants at several of these loci also confer risk
for PCOS in women of European ethnicity. The strongest loci in Europeans contain genes
for DENND1A and THADA, with additional associations in loci containing the LHCGR and FSHR, YAP1 and RAB5/SUOX. The next steps in uncovering the pathophysiology borne out by these loci and variants
will include mapping to determine the causal variant and gene, phenotype studies to
determine whether these regions are associated with particular features of PCOS and
functional studies of the causal variant to determine the direct cause of PCOS based
on the underlying genetics. The next years will be very exciting times as groups from
around the world come together to further elucidate the genetic origins of PCOS.
Keywords
genome-wide association - gonadotropins - hyperandrogenism
