Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis

We conducted a genome-wide association scan (GWAS) of endometriosis using 25.5 million sequence variants detected through whole-genome sequencing (WGS) of 8,453 Icelanders and imputed into 1,840 cases and 129,016 control women, followed by testing of associated variants in Danish samples. Here we report the discovery of a new endometriosis susceptibility locus on 4q12 (rs17773813[G], OR=1.28; P =3.8 × 10 −11 ), upstream of KDR encoding vascular endothelial growth factor receptor 2 (VEGFR2). The variant correlates with disease severity ( P =0.0046) when moderate/severe endometriosis cases are tested against minimal/mild cases. We further report association of rs519664[T] in TTC39B on 9p22 with endometriosis ( P =4.8 × 10 −10 ; OR=1.29). The involvement of KDR in endometriosis risk highlights the importance of the VEGF pathway in the pathogenesis of the disease. Endometriosis is a common gynaecological disease but the underlying pathogenesis is poorly understood, however there is a strong familial component. Here the authors conduct a genome wide association study and identify a novel susceptibility locus that correlates with disease severity.