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

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dc.contributor.authorOrg, Elin
dc.contributor.authorEyheramendy, Susana
dc.contributor.authorJuhanson, Peeter
dc.contributor.authorGieger, Christian
dc.contributor.authorLichtner, Peter
dc.contributor.authorKlopp, Norman
dc.contributor.authorVeldre, Gudrun
dc.contributor.authorDoering, Angela
dc.contributor.authorViigimaa, Margus
dc.contributor.authorSober, Siim
dc.contributor.authorTomberg, Kaert
dc.contributor.authorEckstein, Gertrud
dc.contributor.authorKelgo, Piret
dc.contributor.authorRebane, Tiina
dc.contributor.authorShaw Hawkins, Sue
dc.contributor.authorHoward, Philip
dc.contributor.authorOnipinla, Abiodun
dc.contributor.authorDobson, Richard J.
dc.contributor.authorNewhouse, Stephen J.
dc.contributor.authorBrown, Morris
dc.contributor.authorDominiczak, Anna
dc.contributor.authorConnell, John
dc.contributor.authorSamani, Nilesh
dc.contributor.authorFarrall, Martin
dc.contributor.authorCaulfield, Mark J.
dc.contributor.authorMunroe, Patricia B.
dc.contributor.authorIllig, Thomas
dc.contributor.authorWichmann, H. Erich
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorLaan, Maris
dc.contributor.authorKORA
dc.contributor.authorBRIGHT
dc.date.accessioned2024-01-10T13:13:18Z
dc.date.available2024-01-10T13:13:18Z
dc.date.issued2009
dc.description.abstractHypertension 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.
dc.description.funderWellcome Trust International Senior Research Fellowship
dc.description.funderAlexander-von-Humboldt Foundation partnership
dc.description.funderEstonian Ministry of Education and Science core
dc.description.funderHHMI International Scholarship
dc.description.funderEstonian Science Foundation
dc.description.funderHelmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
dc.description.funderGerman Federal Ministry of Education and Research (BMBF)
dc.description.funderGerman National Genome Research Network (NGFN)
dc.description.funderMedical Research Council of Great Britain
dc.description.funderBritish Heart Foundation
dc.description.funderWellcome Trust
dc.description.funderBarts and The London Genome Centre
dc.description.funderBritish Heart Foundation Chairholders
dc.description.funderMedical Research Council
dc.fechaingreso.objetodigital2024-04-30
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1093/hmg/ddp135
dc.identifier.eissn1460-2083
dc.identifier.issn0964-6906
dc.identifier.pubmedidMEDLINE:19304780
dc.identifier.urihttps://doi.org/10.1093/hmg/ddp135
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78290
dc.identifier.wosidWOS:000266349400016
dc.information.autorucMatemática;Eyheramendy S;S/I;82611
dc.issue.numero12
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final2296
dc.pagina.inicio2288
dc.publisherOXFORD UNIV PRESS
dc.revistaHUMAN MOLECULAR GENETICS
dc.rightsacceso abierto
dc.subjectMOLECULE T-CADHERIN
dc.subjectESSENTIAL-HYPERTENSION
dc.subjectASSOCIATION
dc.subjectVASCULATURE
dc.subjectEXPRESSION
dc.subjectCANCER
dc.subjectSET
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGenome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations
dc.typeartículo
dc.volumen18
sipa.codpersvinculados82611
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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