Human Molecular Genetics Advance Access originally published online on March 20, 2009
Human Molecular Genetics 2009 18(12):2288-2296; doi:10.1093/hmg/ddp135
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Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations
1 Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia 2 Institute of Epidemiology 3 Institute of Human Genetics, Helmholtz Zentrum München, German Research Centre for Environmental Health, 85764 Neuherberg, Germany 4 Department of Statistics, Pontificia Universidad Catolica de Chile, Vicuña Mackena 4860, Santiago, Chile 5 Department of Cardiology, University of Tartu, L. Puusepa 1a, 50406 Tartu, Estonia 6 Centre of Cardiology, North Estonia Medical Centre, Sütiste tee 19, 13419 Tallinn, Estonia 7 Clinical Pharmacology and the Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London EC1M 6BQ, UK 8 Clinical Pharmacology Unit, Addenbrookes Hospital, University of Cambridge, Cambridge CB2 2QQ, UK 9 Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK 10 Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Groby Road, Leicester LE3 9QP, UK 11 Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK 12 Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, D-81377 Munich, Germany 13 Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
* To whom correspondence should be addressed. Tel: +372 7375008; Fax: +372 7420286; Email: maris.laan{at}ut.ee
Received December 1, 2008; Revised February 4, 2009; Accepted March 18, 2009
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 x 10–5, effect –1.40 mmHg; SBP, P = 0.007, effect –1.56 mmHg; HYP, P = 5.30 x 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.
Kooperative Gesundheitsforschung in der Region Augsburg (KORA), the British Genetics of Hypertension study (BRIGHT), additional consortium contributors are given in Supplementary Material.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.