Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations.
Org E., Eyheramendy S., Juhanson P., Gieger C., Lichtner P., Klopp N., Veldre G., Döring A., Viigimaa M., Sõber S., Tomberg K., Eckstein G., KORA None., Kelgo P., Rebane T., Shaw-Hawkins S., Howard P., Onipinla A., Dobson RJ., Newhouse SJ., Brown M., Dominiczak A., Connell J., Samani N., Farrall M., BRIGHT None., Caulfield MJ., Munroe PB., Illig T., Wichmann HE., Meitinger T., Laan M.
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.