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Ellinghaus, E.* ; Ellinghaus, D.* ; Krusche, P.* ; Greiner, A.* ; Schreiber, C.* ; Nikolaus, S.* ; Gieger, C. ; Strauch, K. ; Lieb, W.* ; Rosenstiel, P.* ; Frings, N.* ; Fiebig, A.* ; Schreiber, S.* ; Franke, A.*

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

Sci. Rep. 7:45652 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Primary Varicose-veins; Vasa Vasorum; K+ Channels; Cutis Laxa; In-vivo; Variants; Population; Mutation; Heritability; Angiogenesis
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Journal Scientific Reports
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 45652 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)