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

Nat Commun. 2016 Jul 25:7:12350. doi: 10.1038/ncomms12350.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 17 / genetics
  • Endometriosis / genetics*
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Lipoproteins, HDL / genetics*
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*


  • Lipoproteins, HDL
  • Neoplasm Proteins
  • TTC39B protein, human
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2