New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

Aldi T. Kraja; James P. Cook; Helen R. Warren; Praveen Surendran; Chunyu Liu; Evangelos Evangelou; Alisa K. Manning; Niels Grarup; Fotios Drenos; Xueling Sim; Albert Vernon Smith; Najaf Amin; Alexandra I.F. Blakemore; Jette Bork-Jensen; Ivan Brandslund; Aliki Eleni Farmaki; Cristiano Fava; Teresa Ferreira; Karl Heinz Herzig; Ayush Giri; Franco Giulianini; Megan L. Grove; Xiuqing Guo; Sarah E. Harris; Christian T. Have; Aki S. Havulinna; He Zhang; Marit E. Jørgensen; Anne Mari Käräjämäki; Charles Kooperberg; Allan Linneberg; Louis Little; Yongmei Liu; Lori L. Bonnycastle; Yingchang Lu; Reedik Mägi; Anubha Mahajan; Giovanni Malerba; Riccardo E. Marioni; Hao Mei; Cristina Menni; Alanna C. Morrison; Sandosh Padmanabhan; Walter Palmas; Alaitz Poveda; Rainer Rauramaa; Nigel William Rayner; Muhammad Riaz; Ken Rice; Melissa A. Richard; Jennifer A. Smith; Lorraine Southam; Alena Stančáková; Kathleen E. Stirrups; Vinicius Tragante; Tiinamaija Tuomi; Ioanna Tzoulaki; Tibor V. Varga; Stefan Weiss; Andrianos M. Yiorkas; Robin Young; Weihua Zhang; Michael R. Barnes; Claudia P. Cabrera; He Gao; Michael Boehnke; Eric Boerwinkle; John C. Chambers; John M. Connell; Cramer K. Christensen; Rudolf A. De Boer; Ian J. Deary; George Dedoussis; Panos Deloukas; Anna F. Dominiczak; Marcus Dörr; Roby Joehanes; Todd L. Edwards; Tõnu Esko; Myriam Fornage; Nora Franceschini; Paul W. Franks; Giovanni Gambaro; Leif Groop; Göran Hallmans; Torben Hansen; Caroline Hayward; Oksa Heikki; Erik Ingelsson; Jaakko Tuomilehto; Marjo Riitta Jarvelin; Sharon L.R. Kardia; Fredrik Karpe; Jaspal S. Kooner; Timo A. Lakka; Claudia Langenberg; Lars Lind; Ruth J.F. Loos; Markku Laakso; Mark I. McCarthy; Olle Melander; Karen L. Mohlke; Andrew P. Morris; Colin N.A. Palmer; Oluf Pedersen; Ozren Polasek; Neil R. Poulter; Michael A. Province; Bruce M. Psaty; Paul M. Ridker; Jerome I. Rotter; Igor Rudan; Veikko Salomaa; Nilesh J. Samani; Peter J. Sever; Tea Skaaby; Jeanette M. Stafford; John M. Starr; Pim Van Der Harst; Peter Van Der Meer; Cornelia M. Van Duijn; Anne Claire Vergnaud; Vilmundur Gudnason; Nicholas J. Wareham; James G. Wilson; Cristen J. Willer; Daniel R. Witte; Eleftheria Zeggini; Danish Saleheen; Adam S. Butterworth; John Danesh; Folkert W. Asselbergs; Louise V. Wain; Georg B. Ehret; Daniel I. Chasman; Mark J. Caulfield; Paul Elliott; Cecilia M. Lindgren; Daniel Levy; Christopher Newton-Cheh; Patricia B. Munroe; Joanna M.M. Howson; CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group

doi:10.1161/CIRCGENETICS.117.001778

Back

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

Journal article

Open access

Peer reviewed

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

Aldi T. Kraja, James P. Cook, Helen R. Warren, Praveen Surendran, Chunyu Liu, Evangelos Evangelou, Alisa K. Manning, Niels Grarup, Fotios Drenos, Xueling Sim, …

Circulation. Cardiovascular genetics, Vol.10(5), pp.e001778-e001778

01/10/2017

DOI: https://doi.org/10.1161/CIRCGENETICS.117.001778

PMCID: PMC5776077

PMID: 29030403

Abstract

Basic Medicine

blood pressure

Cardiac and Cardiovascular Systems

Clinical Medicine

Endocrinology and Diabetes

Endokrinologi och diabetes

exome

genetics

genotype

Kardiologi

Klinisk medicin

Medical and Health Sciences

Medical Genetics

Medicin och hälsovetenskap

Medicinsk genetik

Medicinska och farmaceutiska grundvetenskaper

sample size

Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant. Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

Files and links (1)

url

https://doi.org/10.1161/CIRCGENETICS.117.001778View

Published (Version of record) Open

Metrics

1 Record Views

See more details

Details

Title: New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals
Creators - without role: Aldi T. Kraja - Washington University in St. Louis
James P. Cook - University of Liverpool
Helen R. Warren - Queen Mary University
Praveen Surendran - University of Cambridge
Chunyu Liu - Framingham Heart Study
Evangelos Evangelou - Imperial College London
Alisa K. Manning - Boston University
Niels Grarup - University of Copenhagen
Fotios Drenos - University of Bristol
Xueling Sim - University of Michigan
Albert Vernon Smith - University of Iceland
Najaf Amin - Erasmus MC
Alexandra I.F. Blakemore - Imperial College London
Jette Bork-Jensen - University of Copenhagen
Ivan Brandslund - University of Southern Denmark
Aliki Eleni Farmaki - Harokopio University of Athens
Cristiano Fava - University of Verona
Teresa Ferreira - Wellcome Centre for Human Genetics
Karl Heinz Herzig - University of Oulu
Ayush Giri - Vanderbilt University
Franco Giulianini - Brigham and Women's Hospital
Megan L. Grove - University of Texas
Xiuqing Guo - University of California, Los Angeles
Sarah E. Harris - University of Edinburgh
Christian T. Have - University of Copenhagen
Aki S. Havulinna - Department of Social Services and Health Care, Jakobstad
He Zhang - University of Michigan
Marit E. Jørgensen - Steno Diabetes Center
Anne Mari Käräjämäki - Vaasa Central Hospital
Charles Kooperberg - Hutchinson
Allan Linneberg - Research Centre for Prevention and Health
Louis Little - Queen Mary University
Yongmei Liu - Atrium Health Wake Forest Baptist
Lori L. Bonnycastle - National Human Genome Research Institute
Yingchang Lu - Icahn School of Medicine at Mount Sinai
Reedik Mägi - University of Tartu
Anubha Mahajan - Wellcome Centre for Human Genetics
Giovanni Malerba - University of Verona
Riccardo E. Marioni - University of Edinburgh
Hao Mei - University of Mississippi Medical Center
Cristina Menni - King's College London
Alanna C. Morrison - University of Texas
Sandosh Padmanabhan - University of Glasgow
Walter Palmas - Columbia University
Alaitz Poveda - Genetic and Molecular Epidemiology
Rainer Rauramaa - University of Eastern Finland
Nigel William Rayner - Wellcome Sanger Institute
Muhammad Riaz - Glenfield Hospital
Ken Rice
Melissa A. Richard - The University of Texas Health Science Center at Houston
Jennifer A. Smith - University of Michigan
Lorraine Southam - Wellcome Centre for Human Genetics
Alena Stančáková - University of Eastern Finland
Kathleen E. Stirrups - Queen Mary University
Vinicius Tragante - University Medical Center Utrecht
Tiinamaija Tuomi - Umeå University
Ioanna Tzoulaki - University of Ioannina
Tibor V. Varga - University of Eastern Finland
Stefan Weiss - German Centre for Cardiovascular Research
Andrianos M. Yiorkas - Brunel University London
Robin Young - University of Cambridge
Weihua Zhang - Ealing Hospital
Michael R. Barnes - Queen Mary University
Claudia P. Cabrera - Queen Mary University
He Gao - Imperial College London
Michael Boehnke - University of Michigan
Eric Boerwinkle - Baylor College of Medicine
John C. Chambers - Ealing Hospital
John M. Connell - University of Dundee
Cramer K. Christensen - Lillebaelt Hospital
Rudolf A. De Boer - University Medical Center Groningen
Ian J. Deary - University of Edinburgh
George Dedoussis - Harokopio University of Athens
Panos Deloukas - Queen Mary University
Anna F. Dominiczak - University of Glasgow
Marcus Dörr - University Medicine Greifswald
Roby Joehanes - Hebrew SeniorLife
Todd L. Edwards - Vanderbilt University
Tõnu Esko - University of Tartu
Myriam Fornage - The University of Texas Health Science Center at Houston
Nora Franceschini - University of North Carolina
Paul W. Franks - Umeå University
Giovanni Gambaro - Università Cattolica del Sacro Cuore
Leif Groop - Institute for Molecular Medicine Finland
Göran Hallmans - Umeå University
Torben Hansen - University of Copenhagen
Caroline Hayward - University of Edinburgh
Oksa Heikki - Tampere University Hospital
Erik Ingelsson - Uppsala University
Jaakko Tuomilehto - King Abdulaziz University
Marjo Riitta Jarvelin - Imperial College London
Sharon L.R. Kardia - University of Michigan
Fredrik Karpe - University of Oxford
Jaspal S. Kooner - Imperial College London
Timo A. Lakka - University of Eastern Finland
Claudia Langenberg - University of Cambridge
Lars Lind - Uppsala University
Ruth J.F. Loos - Icahn School of Medicine at Mount Sinai
Markku Laakso - University of Eastern Finland
Mark I. McCarthy - Wellcome Centre for Human Genetics
Olle Melander - Cardiovascular Research - Hypertension
Karen L. Mohlke - University of North Carolina
Andrew P. Morris - University of Liverpool
Colin N.A. Palmer - University of Dundee
Oluf Pedersen - University of Copenhagen
Ozren Polasek - University of Split
Neil R. Poulter - Imperial College London
Michael A. Province - Washington University in St. Louis
Bruce M. Psaty - Kaiser Permanente
Paul M. Ridker - Boston University
Jerome I. Rotter - University of California, Los Angeles
Igor Rudan - University of Edinburgh
Veikko Salomaa - Department of Social Services and Health Care, Jakobstad
Nilesh J. Samani - Glenfield Hospital
Peter J. Sever - Imperial College London
Tea Skaaby - Research Centre for Prevention and Health
Jeanette M. Stafford - University of Edinburgh
John M. Starr - Wake Forest University
Pim Van Der Harst - University Medical Center Groningen
Peter Van Der Meer - University Medical Center Groningen
Cornelia M. Van Duijn - Erasmus MC
Anne Claire Vergnaud - Imperial College London
Vilmundur Gudnason - University of Iceland
Nicholas J. Wareham - University of Cambridge
James G. Wilson - University of Mississippi Medical Center
Cristen J. Willer - University of Michigan
Daniel R. Witte - Aarhus University
Eleftheria Zeggini - Wellcome Sanger Institute
Danish Saleheen - Centre for Non-Communicable Diseases
Adam S. Butterworth - University of Cambridge
John Danesh - Wellcome Sanger Institute
Folkert W. Asselbergs - University Medical Center Utrecht
Louise V. Wain - University of Leicester
Georg B. Ehret - Geneva University Hospital
Daniel I. Chasman - Brigham and Women's Hospital
Mark J. Caulfield - Queen Mary University
Paul Elliott - Imperial College London
Cecilia M. Lindgren - Broad Institute
Daniel Levy - National Heart Lung and Blood Institute
Christopher Newton-Cheh - Broad Institute
Patricia B. Munroe - Queen Mary University
Joanna M.M. Howson - University of Cambridge
CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group
Publication Details: Circulation. Cardiovascular genetics, Vol.10(5), pp.e001778-e001778
Identifiers: 9937520708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article