Genome-wide association analysis for chronic venous disease identifies EFEMP1 and KCNH8 as susceptibility loci View Full Text


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Article Info

DATE

2017-12

AUTHORS

Eva Ellinghaus, David Ellinghaus, Petra Krusche, Aljoscha Greiner, Claudia Schreiber, Susanna Nikolaus, Christian Gieger, Konstantin Strauch, Wolfgang Lieb, Philip Rosenstiel, Norbert Frings, Andreas Fiebig, Stefan Schreiber, Andre Franke

ABSTRACT

Chronic venous disease (CVD) is a multifactorial condition representing one of the most common disorders among populations of Western countries. The heritability of about 17% suggests genetic risk factors in CVD etiology. However, so far the genetic causes are unknown. We undertook the hitherto first genome-wide association study (GWAS) for CVD, analyzing more than 1.93 M SNPs in 4,942 German individuals, followed by replication in two independent German data sets. The combined analysis of discovery and replication stages (2,269 cases and 7,765 controls) yielded robust associations within the two genes EFEMP1 and KCNH8 (rs17278665, rs727139 with P < 5 × 10-8), and suggestive association within gene SKAP2 (rs2030136 with P < 5 × 10-7). Association signals of rs17278665 and rs727139 reside in regions of low linkage disequilibrium containing no other genes. Data from the ENCODE and Roadmap Epigenomics projects show that tissue specific marks overlap with the variants. SNPs rs17278665 and rs2030136 are known eQTLs. Our study demonstrates that GWAS are a valuable tool to study the genetic component of CVD. With our approach, we identified two novel genome-wide significant susceptibility loci for this common disease. Particularly, the extracellular matrix glycoprotein EFEMP1 is promising for future functional studies due to its antagonistic role in vessel development and angiogenesis. More... »

PAGES

45652

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep45652

    DOI

    http://dx.doi.org/10.1038/srep45652

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084511449

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28374850


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