Open AccessCommon variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis
Author(s) -
Valgerður Steinthórsdóttir,
Guðmar Þorleifsson,
Kristrun Aradottir,
Bjarke Feenstra,
Ásgeir Sigurðsson,
Lilja Stefánsdóttir,
Anna M. Kristinsdottir,
Florian Zink,
Gisli H. Halldorsson,
Nete Munk Nielsen,
Frank Geller,
Mads Melbye,
Daníel F. Guðbjartsson,
Reynir Tómas Geirsson,
Unnur Þorsteinsdóttir,
Kāri Stefánsson
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms12350
Subject(s) - endometriosis , genome wide association study , locus (genetics) , genetic association , disease , pathogenesis , genetics , biology , single nucleotide polymorphism , medicine , oncology , cancer research , gene , genotype
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.