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 re...

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Detalles Bibliográficos
Autores principales: Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Aradottir, Kristrun, Feenstra, Bjarke, Sigurdsson, Asgeir, Stefansdottir, Lilja, Kristinsdottir, Anna M., Zink, Florian, Halldorsson, Gisli H., Munk Nielsen, Nete, Geller, Frank, Melbye, Mads, Gudbjartsson, Daniel F., Geirsson, Reynir T., Thorsteinsdottir, Unnur, Stefansson, Kari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962463/
https://www.ncbi.nlm.nih.gov/pubmed/27453397
http://dx.doi.org/10.1038/ncomms12350
Descripción
Sumario: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.

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