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. 2016 Jul 25;7:12350.
doi: 10.1038/ncomms12350.

Common Variants Upstream of KDR Encoding VEGFR2 and in TTC39B Associate With Endometriosis

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Common Variants Upstream of KDR Encoding VEGFR2 and in TTC39B Associate With Endometriosis

Valgerdur Steinthorsdottir et al. Nat Commun. .
Free PMC article


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.

Conflict of interest statement

All deCODE authors are employees of the biotechnology firm deCODE Genetics, a subsidiary of AMGEN. The remaining authors declare no competing financial interests.


Figure 1
Figure 1. Locus plot for KDR and TTC39B loci in endometriosis.
Data are based on association with all endometriosis (expressed as −log10(P value) derived by logistic regression) for variants identified by WGS and imputation. Variants are plotted in colours according to their r2 values relative to the index SNP as indicated. Recombination rates, in cM/Mb, estimated from the International HapMap Project are plotted as red lines. The lower panel sections shows the locations of RefSeq genes and the chromosomal position (NCBI hg38, Build 38). The region shown is ±500 kb from the index SNP. (a) KDR locus on chr4q12; index SNP rs17773813. (b) TTC39B locus on chr9p22; index SNP rs519664.

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