Genome-wide association studies on endometriosis and endometriosis-related infertility

Endometriosis affects ∼10% of women of reproductive age. It is characterized by the growth of endometrial-like tissue outside the uterus and is frequently associated with severe pain and infertility. We performed the largest endometriosis genome-wide association study (GWAS) to date, with 37,183 cases and 251,258 controls. All women were of European ancestry. We also performed the first GWAS of endometriosis-related infertility, including 2,969 cases and 3,770 controls. Our endometriosis GWAS study replicated, at genome-wide significance, seven loci identified in previous endometriosis GWASs ( CELA3A-CDC42, SYNE1, KDR, FSHB-ARL14EP, GREB1, ID4 , and CEP112 ) and identified seven new candidate loci with genome-wide significance ( NGF, ATP1B1-F5, CD109, HEY2, OSR2-VPS13B, WT1 , and TEX11-SLC7A3 ). No loci demonstrated genome-wide significance for endometriosis-related infertility, however, the three most strongly associated loci ( MCTP1, EPS8L3-CSF1 , and LPIN1 ) were in or near genes associated with female fertility or embryonic lethality in model organisms. These results reveal new candidate genes with potential involvement in the pathophysiology of endometriosis and endometriosis-related infertility.