Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations

Elin Org, Susana Eyheramendy, Peeter Juhanson, Christian Gieger, Peter Lichtner, Norman Klopp, Gudrun Veldre, Angela Döring, Margus Viigimaa, Siim Sõber, Kärt Tomberg, Gertrud Eckstein, Piret Kelgo, Tiina Rebane, Sue Shaw-Hawkins, Philip Howard, Abiodun Onipinla, Richard J. Dobson, Stephen J. Newhouse, Morris BrownAnna Dominiczak, John Connell, Nilesh Samani, Martin Farrall, Mark J. Caulfield, Patricia B. Munroe, Thomas Illig, H. Erich Wichmann, Thomas Meitinger, Maris Laan

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Hypertension is a complex disease that affects a large proportion of adult population. Although approximately half of the inter-individual variance in blood pressure (BP) level is heritable, identification of genes responsible for its regulation has remained challenging. Genome-wide association study (GWAS) is a novel approach to search for genetic variants contributing to complex diseases. We conducted GWAS for three BP traits [systolic and diastolic blood pressure (SBP and DBP); hypertension (HYP)] in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) S3 cohort (n = 1644) recruited from general population in Southern Germany. GWAS with 395 912 single nucleotide polymorphisms (SNPs) identified an association between BP traits and a common variant rs11646213 (T/A) upstream of the CDH13 gene at 16q23.3. The initial associations with HYP and DBP were confirmed in two other European population-based cohorts: KORA S4 (Germans) and HYPEST (Estonians). The associations between rs11646213 and three BP traits were replicated in combined analyses (dominant model: DBP, P = 5.55 × 10-5, effect -1.40 mmHg; SBP, P = 0.007, effect -1.56 mmHg; HYP, P = 5.30 × 10-8, OR = 0.67). Carriers of the minor allele A had a decreased risk of hypertension. A non-significant trend for association was also detected with severe family based hypertension in the BRIGHT sample (British). The novel susceptibility locus, CDH13, encodes for an adhesion glycoprotein T-cadherin, a regulator of vascular wall remodeling and angiogenesis. Its function is compatible with the BP biology and may improve the understanding of the pathogenesis of hypertension.

Original languageEnglish
Pages (from-to)2288-2296
Number of pages9
JournalHuman Molecular Genetics
Volume18
Issue number12
DOIs
StatePublished - 2009

Fingerprint

Dive into the research topics of 'Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations'. Together they form a unique fingerprint.

Cite this