title: Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis.
abstract: 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.
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Steinthorsdottir
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.affiliation: Department of Obstetrics and Gynecology, Landspitali University Hospital, 101 Reykjavik, Iceland.
authors.forename: Kristrun
authors.initials: K
authors.lastname: Aradottir
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark.
authors.forename: Bjarke
authors.identifier: http://orcid.org/0000-0003-1478-649X
authors.initials: B
authors.lastname: Feenstra
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
authors.forename: Asgeir
authors.initials: A
authors.lastname: Sigurdsson
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
authors.forename: Lilja
authors.initials: L
authors.lastname: Stefansdottir
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kristinsdottir
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
authors.forename: Florian
authors.initials: F
authors.lastname: Zink
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
authors.forename: Gisli H
authors.initials: GH
authors.lastname: Halldorsson
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark.
authors.forename: Nete
authors.initials: N
authors.lastname: Munk Nielsen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Geller
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark.|Department of Clinical Medicine, University of Copenhagen, DK-2100 Copenhagen, Denmark.|Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.affiliation: Department of Obstetrics and Gynecology, Landspitali University Hospital, 101 Reykjavik, Iceland.
authors.forename: Reynir T
authors.initials: RT
authors.lastname: Geirsson
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.|Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: deCODE Genetics/Amgen, 101 Reykjavik, Iceland.|Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D008075:Lipoproteins, HDL; D009363:Neoplasm Proteins; C000628194:TTC39B protein, human; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2