Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations.
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.
Org
Elin
E
Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
Eyheramendy
Susana
S
Juhanson
Peeter
P
Gieger
Christian
C
Lichtner
Peter
P
Klopp
Norman
N
Veldre
Gudrun
G
Döring
Angela
A
Viigimaa
Margus
M
Sõber
Siim
S
Tomberg
Kärt
K
Eckstein
Gertrud
G
Kelgo
Piret
P
Rebane
Tiina
T
Shaw-Hawkins
Sue
S
Howard
Philip
P
Onipinla
Abiodun
A
Dobson
Richard J
RJ
Newhouse
Stephen J
SJ
Brown
Morris
M
Dominiczak
Anna
A
Connell
John
J
Samani
Nilesh
N
Farrall
Martin
M
Caulfield
Mark J
MJ
Munroe
Patricia B
PB
Illig
Thomas
T
Wichmann
H-Erich
HE
Meitinger
Thomas
T
Laan
Maris
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D015820:Cadherins / Q000235:genetics*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*; D055815:Young Adult
D015820:Cadherins; C099972:H-cadherin