ArticleHeart rhythm2017
Fine mapping of QT interval regions in global populations refines previously identified QT interval loci and identifies signals unique to African and Hispanic descent populations.
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Article in Heart rhythm, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 3 of them syntheses that pooled it.
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17 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus atHeart (British Cardiac Society) · 2018Pooled it
- GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals.Scientific reports · 2017Pooled it
- Trans-ethnic meta-regression of genome-wide association studies accounting for ancestry increases power for discovery and improves fine-mapping resolution.Human molecular genetics · 2017Pooled it
- Characterization of novel arrhythmogenic patterns arising secondary to heterogeneous expression and activation of Nav1.8.Frontiers in cardiovascular medicine · 2025Article
- Arrhythmias and ion channelopathies causing sudden cardiac death in Hispanic/Latino and Indigenous populations.Journal of cardiovascular electrophysiology · 2024Review
- Type 2 Diabetes Modifies the Association of CAD Genomic Risk Variants With Subclinical Atherosclerosis.Circulation. Genomic and precision medicine · 2023Article
- Morphological and behavioral analysis of Slc35f1-deficient mice revealed no neurodevelopmental phenotype.Brain structure & function · 2023Article
- Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.Circulation · 2023Article
- Analysis of putative cis-regulatory elements regulating blood pressure variation.Human molecular genetics · 2020Article
- Importance of Genetic Studies of Cardiometabolic Disease in Diverse Populations.Circulation research · 2020Review
- Evaluating the promise of inclusion of African ancestry populations in genomics.NPJ genomic medicine · 2020Review
- The Future of Genomic Studies Must Be Globally Representative: Perspectives from PAGE.Annual review of genomics and human genetics · 2019Review
- Article
- Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study.Human molecular genetics · 2018Article
- Deleterious protein-altering mutations in the SCN10A voltage-gated sodium channel gene are associated with prolonged QT.Clinical genetics · 2018Article
- Putting a finer point on it-Resolving QT loci using multiethnic studies.Heart rhythm · 2017Article
- Genomics of Reproductive Traits and Cardiometabolic Disease Risk in African American Women.Nursing researchReview
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Authors and funding
28 authors.
Christy L AveryDepartment of Epidemiology; Carolina Population Center. Electronic address: christy_avery@unc.edu.
Christina L WasselDepartment of Pathology and Laboratory Medicine, College of Medicine, University of Vermont, Burlington, Vermont.
Melissa A RichardInstitute of Molecular Medicine and; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas.
Heather M HighlandDepartment of Epidemiology.
Stephanie BienDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Niha ZubairDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Elsayed Z SolimanDepartment of Epidemiology and Prevention, Epidemiological Cardiology Research Center and; Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston Salem, North Carolina.
Myriam FornageInstitute of Molecular Medicine and; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas.
Suzette J BielinskiDivision of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Ran TaoDepartment of Biostatistics.
Amanda A SeyerleDepartment of Epidemiology.
Sanjiv J ShahDepartment of Preventive Medicine and; Department of Medicine, Northwestern University Feinberg School of Medicine and.
Donald M Lloyd-JonesDepartment of Preventive Medicine and; Department of Medicine, Northwestern University Feinberg School of Medicine and.
Steven BuyskeDepartment of Statistics and Biostatistics and; Department of Genetics, Rutgers University, Piscataway, New Jersey.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.
Wendy S PostDepartment of Medicine and; Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
Lucia A HindorffNational Institutes of Health, National Human Genome Research Institute, Office of Population Genomics, Bethesda, Maryland.
Janina M JeffGenetics and Genomic Sciences, The Charles Bronfman Institute for Personalized Medicine, The Center for Statistical Genetics, and The Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
Ralph V ShohetCenter for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.
Nona SotoodehniaCardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, Washington.
Dan Yu LinDepartment of Biostatistics.
Eric A WhitselDepartment of Epidemiology; Department of Medicine.
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine and; Norris Comprehensive Cancer Center, University of Southern California, Pasadena, California.
Dana C CrawfordDepartment of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Kari E NorthDepartment of Epidemiology; Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Funding
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MVANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MProject 5: ROS, Glutathione and Vascular Response to Diesel ExhaustP50ES015915 · NIEHS · UNIVERSITY OF WASHINGTON · PI KAVANAGH, TERRANCE J · 2008 to 2012
$11.8MMulti-Ethnic Study of Atherosclerosis (MESA) StudyR01HL071205 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ROTTER, JEROME I · 2003 to 2007
$10.4MVanderbilt/Meharry Initiative for Minority Student DvptR25GM062459 · NIGMS · VANDERBILT UNIVERSITY · PI VELEZ EDWARDS, DIGNA R · 2002 to 2020
$10.4MCardiovascular Epidemiology Training GrantT32HL007055 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Wayne D. Rosamond · 1986 to 2026
$10.0MEpidemiology of putative genuine genetic variant: The Women's Health IntiativeU01HG004790 · NHGRI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2008 to 2012
$9.9MNCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001079NCRR NIH HHS UL1 RR024975NHGRI NIH HHS U01 HG004790NHGRI NIH HHS U01 HG004798NHGRI NIH HHS U01 HG004801NHGRI NIH HHS U01 HG004802NHGRI NIH HHS U01 HG004803NHGRI NIH HHS U01 HG007376NHGRI NIH HHS U01 HG007419NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268200900041CNHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI 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 HHSN268201100046CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201300025CNHLBI NIH HHS HHSN268201300026CNHLBI NIH HHS HHSN268201300027CNHLBI NIH HHS HHSN268201300028CNHLBI NIH HHS HHSN268201300029CNHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC065233NHLBI NIH HHS N01 HC065234NHLBI NIH HHS N01 HC065235NHLBI NIH HHS N01 HC065236NHLBI NIH HHS N01 HC065237NHLBI 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 N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL098077NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL111089NHLBI NIH HHS R01 HL116747NHLBI NIH HHS R01 HL120393NHLBI NIH HHS T32 HL007055NHLBI NIH HHS U01 HL080295NIA NIH HHS HHSN271201100004CNIDDK NIH HHS P30 DK063491NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P50 ES015915NIGMS NIH HHS R25 GM062459NIH HHS S10 OD020069WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
Abstract
backgroundThe electrocardiographically measured QT interval (QT) is heritable and its prolongation is an established risk factor for several cardiovascular diseases. Yet, most QT genetic studies have been performed in European ancestral populations, possibly reducing their global relevance.
objectiveTo leverage diversity and improve biological insight, we fine mapped 16 of the 35 previously identified QT loci (46%) in populations of African American (n = 12,410) and Hispanic/Latino (n = 14,837) ancestry.
methodsRacial/ethnic-specific multiple linear regression analyses adjusted for heart rate and clinical covariates were examined separately and in combination after inverse-variance weighted trans-ethnic meta-analysis.
resultsThe 16 fine-mapped QT loci included on the Illumina Metabochip represented 21 independent signals, of which 16 (76%) were significantly (P-value≤9.1×10
conclusionOur findings suggest that a majority of identified SNPs implicate gene regulatory dysfunction in QT prolongation, that the same loci influence variation in QT across global populations, and that additional, novel, population-specific QT signals exist.
Indexed as
Heart Conduction SystemLong QT SyndromeBlack or African AmericanElectrocardiographyGenome-Wide Association StudyHispanic or LatinoHumansLinkage DisequilibriumPolymorphism, Single NucleotideSequence AnalysisUnited StatesAfrican AmericanElectrocardiographyFine mappingHispanic/LatinoQT interval
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