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

Author:
  • 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
Publishing year: 2017-10-01
Language: English
Publication/Series: Circulation: Cardiovascular Genetics
Volume: 10
Issue: 5
Document type: Journal article
Publisher: American Heart Association

Abstract english

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.

Keywords

  • Cardiac and Cardiovascular Systems
  • Endocrinology and Diabetes
  • Medical Genetics
  • blood pressure
  • exome
  • genetics
  • genotype
  • sample size

Other

Published
  • Cardiovascular Research - Hypertension
  • Genetic and Molecular Epidemiology
  • LUDC (Lund University Diabetes Centre)-lup-obsolete
  • Genomics, Diabetes and Endocrinology
  • ISSN: 1942-325X
E-mail: alaitz [dot] poveda [dot] 6461 [at] med [dot] lu [dot] se

Postdoctoral fellow

Genetic and Molecular Epidemiology

+46 40 39 10 32

CRC 60-13-024

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00