Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations..pdf (212.58 kB)
Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations.
journal contribution
posted on 2012-10-24, 09:03 authored by E Org, S Eyheramendy, P Juhanson, C Gieger, P Lichtner, N Klopp, G Veldre, A Döring, M Viigimaa, S Sõber, K Tomberg, G Eckstein, KORA, P Kelgo, T Rebane, S Shaw-Hawkins, P Howard, A Onipinla, RJ Dobson, SJ Newhouse, M Brown, A Dominiczak, J Connell, N Samani, M Farrall, BRIGHT, MJ Caulfield, PB Munroe, T Illig, HE Wichmann, T Meitinger, M LaanHypertension 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.
Funding
The study was supported by Wellcome Trust International Senior Research Fellowship (grant no. 070191/Z/03/Z to M.L.) in Biomedical Science in Central Europe and by Alexander-von-Humboldt Foundation partnership (grant no. V-Fokoop-EST/1051368 and V-Fokoop-1113183 to M.L. and T.M., respectively). In addition, the study has been supported by Estonian Ministry of Education and Science core grant no. 0182721s06, HHMI International Scholarship #55005617 (to M.L.) and Estonian Science Foundation grant no ETF7491 (to E.O.). The KORA Augsburg studies were financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany and supported by grants from the German Federal Ministry of Education and Research (BMBF). The KORA study group consists of H.-E. Wichmann (speaker), A. Peters, C. Meisinger, T. Illig, R. Holle, J. John and co-workers who are responsible for the design and conduct of the KORA studies. Part of this work was financed by the German National Genome Research Network (NGFN). The BRIGHT study and current work are supported by the Medical Research Council of Great Britain (grant no. G9521010D) and the British Heart Foundation (grant no. PG02/128). The Wellcome Trust Case–Control Consortium was funded by the Wellcome Trust (grant no. 076113/B/04/Z). The Barts and The London Charity is funded by the Barts and The London Genome Centre. A.D. and N.S are British Heart Foundation Chairholders. Funding to pay the Open Access publication charges for this article was provided by Wellcome Trust International Senior Research Fellowship (grant no. 070191/Z/03/Z to M.L.) in Biomedical Science in Central Europe.
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Citation
Elin Org, Susana Eyheramendy, Peeter Juhanson, Christian Gieger, Peter Lichtner, Norman Klopp, Gudrun Veldre, Angela Döring, Margus Viigimaa, Siim Sõber, Kärt Tomberg, Gertrud Eckstein, KORA, Piret Kelgo, Tiina Rebane, Sue Shaw-Hawkins, Philip Howard, Abiodun Onipinla, Richard J. Dobson, Stephen J. Newhouse, Morris Brown, Anna Dominiczak, John Connell, Nilesh Samani, Martin Farrall, BRIGHT, Mark J. Caulfield, Patricia B. Munroe, Thomas Illig, H.-Erich Wichmann, Thomas Meitinger, Maris Laan, Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations, Human Molecular Genetics, Volume 18, Issue 12, 15 June 2009, Pages 2288–2296, https://doi.org/10.1093/hmg/ddp135Author affiliation
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular SciencesVersion
- VoR (Version of Record)
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Human Molecular GeneticsVolume
18Issue
12Pagination
2288–2296Publisher
Oxford University Press (OUP)eissn
1460-2083Acceptance date
2009-03-18Copyright date
2009Available date
2009-03-20Publisher DOI
Publisher version
https://academic.oup.com/hmg/article/18/12/2288/643343Language
engAdministrator link
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