Evidence map›Paper›PMID 30012220›Full record

ArticleGenome biology2018

Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.

Bram P Prins, Timothy J Mead, Jennifer A Brody, Gardar Sveinbjornsson, Ioanna Ntalla, Nathan A Bihlmeyer, Marten van den Berg, Jette Bork-Jensen, Stefania Cappellani, Stefan Van Duijvenboden and 103 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 4 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 4 syntheses or guidelines pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  9. An Overview of ADAMTS Proteases.Methods in molecular biology (Clifton, N.J.) · 2026
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  10. Generation of a conditionalMatrix biology plus · 2025
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  20. A Novel Mutation in theInternational journal of molecular sciences · 2023
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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

113 authors at 20 institutions in 11 countries.

Bram P PrinsGenetics Research Centre, Molecular and Clinical Sciences Institute, St George's University of London, London, SW17 0RE, UK.
Timothy J MeadDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
Jennifer A BrodyDepartment of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, 98101, USA.
Gardar SveinbjornssondeCODE genetics/Amgen, Inc., 101, Reykjavik, Iceland.
Ioanna NtallaClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Nathan A BihlmeyerPredoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Marten van den BergDepartment of Medical Informatics Erasmus MC - University Medical Center, P.O. Box 2040, Rotterdam, 3000, CA, The Netherlands.
Jette Bork-JensenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Stefania CappellaniInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137, Trieste, Italy.
Stefan Van DuijvenbodenClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Nikolai T KlenaDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15201, USA.
George C GabrielDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15201, USA.
Xiaoqin LiuDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15201, USA.
Cagri GulecDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15201, USA.
Niels GrarupThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Jeffrey HaesslerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Leanne M HallDepartment of Cardiovascular Sciences, University of Leicester, Cardiovascular Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK.
Annamaria IorioCardiovascular Department, Ospedali Riuniti and University of Trieste, 34100, Trieste, Italy.
Aaron IsaacsCARIM School for Cardiovascular Diseases, Maastricht Center for Systems Biology (MaCSBio), and Department of Biochemistry, Maastricht University, Universiteitssingel 60, Maastricht, 6229 ER, The Netherlands.
Ruifang Li-GaoDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
Honghuang LinDepartment of Medicine, Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, 02118, USA.
Ching-Ti LiuBiostatistics Department, Boston University School of Public Health, Boston, MA, 02118, USA.
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, 33520, Tampere, Finland.
Jonathan MartenMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Hao MeiDepartment of Data Science, School of Population Health, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Martina Müller-NurasyidInstitute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Michele OriniMechanical Engineering Department, University College London, London, WC1E 6BT, UK.
Sandosh PadmanabhanInstitute of Cardiovascular and Medical Sciences, University of Glasgow, BHF GCRC, Glasgow, G12 8TA, UK.
Farid RadmaneshCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA.
Julia RamirezClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Antonietta RobinoInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137, Trieste, Italy.
Molly SchwartzDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15201, USA.
Jessica van SettenDivision Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
Albert V SmithIcelandic Heart Association, 201, Kopavogur, Iceland.
Niek VerweijProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Helen R WarrenClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Stefan WeissInterfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, 17475, Greifswald, Germany.
Alvaro AlonsoDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
David O ArnardeCODE genetics/Amgen, Inc., 101, Reykjavik, Iceland.
Michiel L BotsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Rudolf A de BoerUniversity Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Anna F DominiczakInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Mark EijgelsheimErasmus MC - University Medical Center Rotterdam, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
Patrick T EllinorCardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, 02114, USA.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Stephan B FelixDZHK (German Centre for Cardiovascular Research); Partner site Greifswald, 17475, Greifswald, Germany.
Tamara B HarrisLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, 20892, USA.
Caroline HaywardMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Susan R HeckbertCardiovascular Health Research Unit and the Department of Epidemiology, University of Washington, Seattle, WA, 98101, USA.
Paul L HuangCardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, 02114, USA.
J W JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital, 33521, Tampere, Finland.
Jan A KorsDepartment of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Pier D LambiaseInstitute of Cardiovascular Science, University College London, London, WC1E 6BT, UK.
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, 20892, USA.
Man LiDivision of Nephrology & Hypertension, Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, 84109, USA.
Allan LinnebergResearch Centre for Prevention and Health, Capital Region of Denmark, 2600, Glostrup, Denmark.
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester, Cardiovascular Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK.
Oluf PedersenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Marco PerezDivision of Cardiovascular Medicine, Stanford University, Stanford, CA, 94305, USA.
Annette PetersGerman Centre for Cardiovascular Research (DZHK); partner site: Munich Heart Alliance, Munich, Germany.
Ozren PolasekFaculty of Medicine, University of Split, Split, Croatia.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, 98101, USA.
Olli T RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, Finland.
Kenneth M RiceDepartment of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences and Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Moritz F SinnerDepartment of Medicine I, University Hospital Munich, Ludwig-Maximilians University, Munich, Germany.
Elsayed Z SolimanEpidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Tim D SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Unnur ThorsteinsdottirdeCODE genetics/Amgen, Inc., 101, Reykjavik, Iceland.
Andrew TinkerClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Stella TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
André UitterlindenHuman Genotyping Facility Erasmus MC - University Medical Center Rotterdam, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
Ilonca VaartjesJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Peter van der MeerUniversity Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Uwe VölkerInterfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, 17475, Greifswald, Germany.
Henry VölzkeDZHK (German Centre for Cardiovascular Research); Partner site Greifswald, 17475, Greifswald, Germany.
Melanie WaldenbergerGerman Centre for Cardiovascular Research (DZHK); partner site: Munich Heart Alliance, Munich, Germany.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Zhijun XieTCM Clinical Basis Institute, Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, China.
Folkert W AsselbergsDivision Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
Marcus DörrDZHK (German Centre for Cardiovascular Research); Partner site Greifswald, 17475, Greifswald, Germany.
Cornelia M van DuijnDepartment of Epidemiology, Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam, The Netherlands.
Paolo GaspariniDepartment of Medical, Surgical and Health Sciences, University of Trieste, 34100, Trieste, Italy.
Daniel F GudbjartssondeCODE genetics/Amgen, Inc., 101, Reykjavik, Iceland.
Vilmundur GudnasonIcelandic Heart Association, 201, Kopavogur, Iceland.
Torben HansenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Stefan KääbDepartment of Medicine I, University Hospital Munich, Ludwig-Maximilians University, Munich, Germany.
Jørgen K KantersLaboratory of Experimental Cardiology, University of Copenhagen, 2200, Copenhagen, Denmark.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, 33520, Tampere, Finland.
Henry J LinThe Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Steven A LubitzDivision of Genomic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
Francesco J ContiDubowitz Neuromuscular Centre, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
Christopher H Newton-ChehProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Jonathan RosandCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA.
Igor RudanUsher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Cardiovascular Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK.
Gianfranco SinagraCardiovascular Department, Ospedali Riuniti and University of Trieste, 34100, Trieste, Italy.
Blair H SmithDivision of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
Hilma HolmdeCODE genetics/Amgen, Inc., 101, Reykjavik, Iceland.
Bruno H StrickerDepartment of Epidemiology Erasmus MC - University Medical Center Rotterdam, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
Sheila UliviInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137, Trieste, Italy.
Nona SotoodehniaDivision of Cardiology, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, 98101, USA.
Suneel S ApteDepartment of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
Pim van der HarstUniversity Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Kari StefanssondeCODE genetics/Amgen, Inc., 101, Reykjavik, Iceland.
Patricia B MunroeClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Dan E ArkingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Cecilia W LoDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15201, USA.
Yalda JamshidiGenetics Research Centre, Molecular and Clinical Sciences Institute, St George's University of London, London, SW17 0RE, UK. yjamshid@sgul.ac.uk.ORCID 0000-0003-0151-6482
Erasmus MC · NLQueen Mary University of London · GBUniversity of Copenhagen · DKUniversity of Pittsburgh · USdeCODE Genetics (Iceland) · ISUniversitätsmedizin Greifswald · DEBroad Institute · USHelmholtz Zentrum München · DELeiden University Medical Center · NLUniversity of Washington · USBoston University · USIRCCS Materno Infantile Burlo Garofolo · ITUniversity Medical Center Groningen · NLUniversity of Leicester · GBUniversity of Trieste · ITCleveland Clinic Lerner College of Medicine · USFred Hutch Cancer Center · USGerman Centre for Cardiovascular Research · DEInstitute of Genetics and Cancer · GBJohns Hopkins University · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Tracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI GOMEZ-SANCHEZ, CELSO ENRIQUE · 2016 to 2025
$38.2M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
VERSICAN PROTEOLYSIS AND REGULATION OF VASCULAR SMOOTH MUSCLEP01HL107147 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI DE LA MOTTE, CAROL A. · 2011 to 2017
$16.1M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
British Heart Foundation PG/12/38/29615Medical Research Council MC_PC_17228Medical Research Council MC_PC_U127561128Medical Research Council MC_QA137853Medical Research Council MC_UU_00007/10Medical Research Council MR/N025083/1NCATS NIH HHS UL1 TR001881NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS K23 HL114724NHLBI NIH HHS K24 HL105780NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS P01 HL107147NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL068986NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL104156NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL116747NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL128914NHLBI NIH HHS R01 HL132024NHLBI NIH HHS R01 HL139731NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL098180NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL130114NIAMS NIH HHS F32 AR063548NIA NIH HHS R01 AG023629NIDDK NIH HHS P30 DK063491NIGMS NIH HHS U54 GM115428NIH HHS S10 OD020069NINDS NIH HHS K23 NS059774NINDS NIH HHS R01 NS059727NINDS NIH HHS R01 NS073344Wellcome Trust
6 · The paper itself

Abstract

backgroundGenome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.

resultsHere, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.

conclusionsOur approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

Indexed as

ExomeGenetic LociADAMTS ProteinsAnimalsBlack PeopleConnexin 43ElectrocardiographyExome SequencingFemaleGene ExpressionGene Expression ProfilingGenome-Wide Association StudyHeart Conduction SystemHumansMaleMiceAdamts6 protein, humanADAMTS ProteinsConnexin 43GJA1 protein, humanADAMTS6ConductionExome chipMeta-analysis

Identifiers

PMID30012220
PMCPMC6048820
OpenAlexW2848386833

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.