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 Doering; Margus Viigimaa; Siim Sober; Kaert Tomberg; Gertrud Eckstein; Piret Kelgo; Tiina Rebane; Sue Shaw-Hawkins; Philip Howard; Abiodun Onipinla; Richard J. Dobson; Stephen Newhouse; Morris Brown; Anna Dominiczak; John Connell; Nilesh Samani; Martin Farrall; Mark J. Caulfield; Patricia B. Munroe; Thomas Illig; H. -Erich Wichmann; Thomas Meitinger; Maris Laan

doi:10.1093/hmg/ddp135

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 Doering, Margus Viigimaa, Siim Sober, Kaert Tomberg, Gertrud Eckstein, Piret Kelgo, Tiina Rebane, Sue Shaw-Hawkins, Philip Howard, Abiodun Onipinla, Richard J. Dobson, Stephen 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

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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 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.

Original language	English
Pages (from-to)	2288 - 2296
Number of pages	9
Journal	Human Molecular Genetics
Volume	18
Issue number	12
DOIs	https://doi.org/10.1093/hmg/ddp135
Publication status	Published - 2009

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Org, E., Eyheramendy, S., Juhanson, P., Gieger, C., Lichtner, P., Klopp, N., Veldre, G., Doering, A., Viigimaa, M., Sober, S., Tomberg, K., Eckstein, G., Kelgo, P., Rebane, T., Shaw-Hawkins, S., Howard, P., Onipinla, A., Dobson, R. J., Newhouse, S., ... Laan, M. (2009). Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations. Human Molecular Genetics, 18(12), 2288 - 2296. https://doi.org/10.1093/hmg/ddp135

@article{641d6b1a63364dd4be8b8192fae352ae,

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

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 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.",

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

year = "2009",

doi = "10.1093/hmg/ddp135",

language = "English",

volume = "18",

pages = "2288 -- 2296",

journal = "Human Molecular Genetics",

issn = "1460-2083",

publisher = "Oxford University Press",

number = "12",

}

Org, E, Eyheramendy, S, Juhanson, P, Gieger, C, Lichtner, P, Klopp, N, Veldre, G, Doering, A, Viigimaa, M, Sober, S, Tomberg, K, Eckstein, G, Kelgo, P, Rebane, T, Shaw-Hawkins, S, Howard, P, Onipinla, A, Dobson, RJ , Newhouse, S, Brown, M, Dominiczak, A, Connell, J, Samani, N, Farrall, M, Caulfield, MJ, Munroe, PB, Illig, T, Wichmann, H-E, Meitinger, T & Laan, M 2009, 'Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations', Human Molecular Genetics, vol. 18, no. 12, pp. 2288 - 2296. https://doi.org/10.1093/hmg/ddp135

TY - JOUR

T1 - Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations

AU - Org, Elin

AU - Eyheramendy, Susana

AU - Juhanson, Peeter

AU - Gieger, Christian

AU - Lichtner, Peter

AU - Klopp, Norman

AU - Veldre, Gudrun

AU - Doering, Angela

AU - Viigimaa, Margus

AU - Sober, Siim

AU - Tomberg, Kaert

AU - Eckstein, Gertrud

AU - Kelgo, Piret

AU - Rebane, Tiina

AU - Shaw-Hawkins, Sue

AU - Howard, Philip

AU - Onipinla, Abiodun

AU - Dobson, Richard J.

AU - Newhouse, Stephen

AU - Brown, Morris

AU - Dominiczak, Anna

AU - Connell, John

AU - Samani, Nilesh

AU - Farrall, Martin

AU - Caulfield, Mark J.

AU - Munroe, Patricia B.

AU - Illig, Thomas

AU - Wichmann, H. -Erich

AU - Meitinger, Thomas

AU - Laan, Maris

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddp135

DO - 10.1093/hmg/ddp135

M3 - Article

SN - 1460-2083

VL - 18

SP - 2288

EP - 2296

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 12

ER -

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

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