Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.

Detaljer

Författare
  • Philipp S. Wild
  • Janine F. Felix
  • Arne Schillert
  • Alexander Teumer
  • Ming-Huei Chen
  • Maarten J.G. Leening
  • Uwe Völker
  • Vera Großmann
  • Jennifer A Brody
  • Marguerite R. Irvin
  • Sanjiv J. Shah
  • Setia Pramana
  • Wolfgang Lieb
  • Reinhold Schmidt
  • Alice V Stanton
  • Dörthe Malzahn
  • Albert Vernon Smith
  • Johan Sundström
  • Cosetta Minelli
  • Daniela Ruggiero
  • Leo-Pekka Lyytikäinen
  • Daniel Tiller
  • Claire Monnereau
  • Marco R. Di Tullio
  • Solomon K Musani
  • Alanna C Morrison
  • Tune H. Pers
  • Michael Morley
  • Marcus E Kleber
  • Jayashri Aragam
  • Emelia J Benjamin
  • Joshua C Bis
  • Egbert Bisping
  • Ulrich Broeckel
  • Susan Cheng
  • Jaap W Deckers
  • Fabiola Del Greco M
  • Frank Edelmann
  • Myriam Fornage
  • Lude Franke
  • Nele Friedrich
  • Tamara B Harris
  • Edith Hofer
  • Albert Hofman
  • Jie Huang
  • Alun D. Hughes
  • Mika Kähönen
  • Jochen Kruppa
  • Karl J. Lackner
  • Lars Lannfelt
  • Rafael Laskowski
  • Lenore J Launer
  • Honghuang Lin
  • Cecilia M. Lindgren
  • Christina Loley
  • Calum A. MacRae
  • Deborah Mascalzoni
  • Jamil Mayet
  • Daniel Medenwald
  • Andrew P Morris
  • Christian Müller
  • Martina Müller-Nurasyid
  • Stefania Nappo
  • Sebastian Nuding
  • Teresa Nutile
  • Annette Peters
  • Arne Pfeufer
  • Diana Pietzner
  • Peter P Pramstaller
  • Olli T Raitakari
  • Kenneth M Rice
  • Fernando Rivadeneira
  • Jerome I. Rotter
  • Saku T. Ruohonen
  • Ralph L. Sacco
  • Tandaw E. Samdarshi
  • Helena Schmidt
  • Andrew S.P. Sharp
  • Denis C. Shields
  • Rossella Sorice
  • Nona Sotoodehnia
  • Bruno H Stricker
  • Praveen Surendran
  • Simon Thom
  • Anna M. Töglhofer
  • André G Uitterlinden
  • Rolf Wachter
  • Henry Völzke
  • Andreas Ziegler
  • Thomas Münzel
  • Winfried März
  • Thomas P Cappola
  • Joel N. Hirschhorn
  • Gary F. Mitchell
  • Nicholas L Smith
  • Ervin R Fox
  • Nicole D. Dueker
  • Vincent W. V. Jaddoe
  • Martin Russ
  • Terho Lehtimäki
  • Marina Ciullo
  • Andrew A Hicks
  • Lars Lind
  • Vilmundur Gudnason
  • Burkert Pieske
  • Anthony J. Barron
  • Robert Zweiker
  • Heribert Schunkert
  • Erik Ingelsson
  • Kiang Liu
  • Donna K. Arnett
  • Bruce M. Psaty
  • Stefan Blankenberg
  • Martin G. Larson
  • Stephan B Felix
  • Oscar H. Franco
  • Tanja Zeller
  • Ramachandran S. Vasan
  • Marcus Dörr
Enheter & grupper
Externa organisationer
  • University of Mainz
  • German Centre for Cardiovascular Research
  • Erasmus University Medical Center
  • Boston University
  • University of Washington
  • University of Alabama
  • Karolinska Institute
  • University of Kiel
  • Medical University of Graz
  • Royal College of Surgeons in Ireland
  • University Medical Center Göttingen
  • Icelandic Heart Association
  • University of Iceland
  • Uppsala universitet, Historiska institutionen
  • Imperial College London
  • CNR
  • University of Tampere
  • Martin-Luther-Universität Halle-Wittenberg
  • Broad Institute
  • Columbia University
  • University of Mississippi Medical Center
  • University of Texas
  • Boston Children's Hospital
  • University of Copenhagen
  • Danish Serum Institute, Copenhagen
  • University of Pennsylvania
  • Heidelberg University
  • Harvard Medical School
  • Framingham Heart Study
  • Medical College of Wisconsin
  • Brigham and Women's Hospital / Harvard Medical School
  • European Academy Bolzano
  • Charité Universitätsmedizin Berlin
  • University of Groningen
  • University Medicine Greifswald
  • National Institute on Aging, United States
  • Boston VA Research Institute
  • University College London
  • Tampere University Hospital
  • University of Veterinary Medicine Hannover
  • Universitätsmedizin Mainz
  • Skåne University Hospital
  • Harvard University
  • Hammersmith Hospital
  • Wellcome Trust Centre for Human Genetics
  • University of Liverpool
  • University Medical Center Hamburg-Eppendorf
  • World Orthopaedic Concern
  • Helmholtz Zentrum München
  • Turku University Hospital
  • University of Turku
  • University of California, Los Angeles
  • University of Miami
  • University of Exeter
  • University College Dublin
  • Istituto Neurologico Mediterraneo Neuromed
  • Dutch Healthcare Inspectorate
  • University of KwaZulu-Natal
  • Cardiovascular Engineering Inc.
  • Group Health Cooperative
  • U.S. Department of Veterans Affairs
  • Helios Amper-klinikum Dachau
  • Fimlab Laboratories
  • German Heart Center Berlin
  • Technical University of Munich
  • Stanford University
  • Northwestern University
  • Massachusetts General Hospital
  • British Columbia Children's Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
Originalspråkengelska
Sidor (från-till)1798-1812
Antal sidor15
TidskriftJournal of Clinical Investigation
Volym127
Utgivningsnummer5
StatusPublished - 2017 maj 1
PublikationskategoriForskning
Peer review utfördJa