Journal article
GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations
PloS one, Vol.14(6), pp.e0217796-e0217796
2019
DOI: 10.1371/journal.pone.0217796
PMCID: PMC6599128
PMID: 31251759
Abstract
The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored.
We performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted meta-analysis.
We identified six loci associated with QRS (P<5x10-8), including two novel loci: MYOCD, a nuclear protein expressed in the heart, and SYT1, an integral membrane protein. The top SNP in the MYOCD locus, intronic SNP rs16946539, was found in Hispanics/Latinos with a minor allele frequency (MAF) of 0.04, but is monomorphic in European and African descent populations. The most significant QRS duration association was with intronic SNP rs3922344 (P = 1.19x10-24) in SCN5A/SCN10A. Three other previously identified loci, CDKN1A, VTI1A, and HAND1, also exceeded the GWAS significance threshold among Hispanics/Latinos. A total of 27 of 32 previously identified QRS duration SNPs were shown to generalize in Hispanics/Latinos.
Our QRS duration GWAS, the first in Hispanic/Latino populations, identified two new loci, underscoring the utility of extending large scale genomic studies to currently under-examined populations.
Details
- Title: Subtitle
- GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations
- Creators
- Brenton R Swenson - Cardiovascular Health Research Unit, University of Washington, Seattle, WA, United States of AmericaTin Louie - Department of Biostatistics, University of Washington, Seattle, WA, United States of AmericaHenry J Lin - Division of Medical Genetics, Harbor-UCLA Medical Center, Torrance, CA, United States of AmericaRaúl Méndez-Giráldez - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of AmericaJennifer E Below - Department of Medical Genetics, Vanderbilt University Medical Center, Nashville, TN, United States of AmericaCathy C Laurie - Department of Biostatistics, University of Washington, Seattle, WA, United States of AmericaKathleen F Kerr - Department of Biostatistics, University of Washington, Seattle, WA, United States of AmericaHeather Highland - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States of AmericaTimothy A Thornton - Department of Biostatistics, University of Washington, Seattle, WA, United States of AmericaKelli K Ryckman - Departments of Epidemiology and Pediatrics, University of Iowa, Iowa City, IA, United States of AmericaCharles Kooperberg - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of AmericaElsayed Z Soliman - Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, United States of AmericaAmanda A Seyerle - Carolina Health Informatics Program, University of North Carolina, Chapel Hill, NC, United States of AmericaXiuqing Guo - The Institute for Translational Genomics and Population Sciences, and Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, United States of AmericaKent D Taylor - The Institute for Translational Genomics and Population Sciences, and Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, United States of AmericaJie Yao - The Institute for Translational Genomics and Population Sciences, and Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, United States of AmericaSusan R Heckbert - Department of Epidemiology, University of Washington, Seattle, WA, United States of AmericaDawood Darbar - Division of Cardiology, University of Illinois at Chicago, Chicago, IL, United States of AmericaLauren E Petty - Department of Medical Genetics, Vanderbilt University Medical Center, Nashville, TN, United States of AmericaBarbara McKnight - Department of Biostatistics, University of Washington, Seattle, WA, United States of AmericaSusan Cheng - Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of AmericaNatalie A Bello - Division of Cardiology, Columbia University Medical Center, New York, NY, United States of AmericaEric A Whitsel - Department of Medicine, University of North Carolina, Chapel Hill, NC, United States of AmericaCraig L Hanis - Human Genetics Center, University of Texas, Health Science Center at Houston, Houston, TX, United States of AmericaMike A Nalls - Laboratory of Neurogenetics, National Institute of Aging, Bethesda, MD, United States of AmericaDaniel S Evans - California Pacific Medical Center Research Institute, San Francisco, CA, United States of AmericaJerome I Rotter - The Institute for Translational Genomics and Population Sciences, and Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, United States of AmericaTamar Sofer - Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of AmericaChristy L Avery - Carolina Population Center, University of North Carolina, Chapel Hill, NC, United States of AmericaNona Sotoodehnia - Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.14(6), pp.e0217796-e0217796
- DOI
- 10.1371/journal.pone.0217796
- PMID
- 31251759
- PMCID
- PMC6599128
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Grant note
- N01HC95169 / NHLBI NIH HHS N01HC65235 / NHLBI NIH HHS N01 HC095160 / NHLBI NIH HHS R01 DK073541 / NIDDK NIH HHS HHSN268201600003C / NHLBI NIH HHS UL1 TR001881 / NCATS NIH HHS T32 HL007779 / NHLBI NIH HHS N01 HC065236 / NHLBI NIH HHS HHSN268200782096C / NHGRI NIH HHS HHSN268201600018C / NHLBI NIH HHS N01HC95163 / NHLBI NIH HHS N01 HC095166 / NHLBI NIH HHS N01HC95166 / NHLBI NIH HHS N01 HC095163 / NHLBI NIH HHS R01 HL142302 / NHLBI NIH HHS T32 HL139439 / NHLBI NIH HHS HHSN268201600001C / NHLBI NIH HHS N01 HC095169 / NHLBI NIH HHS HHSN268201500003C / NHLBI NIH HHS HHSN268201300024C / NHLBI NIH HHS N01 HC095159 / NHLBI NIH HHS N01 HC065233 / NHLBI NIH HHS R01 AI085014 / NIAID NIH HHS N01HC65233 / NHLBI NIH HHS HHSN268201500003I / NHLBI NIH HHS T32 HL007055 / NHLBI NIH HHS T32 HL007374 / NHLBI NIH HHS N01HC65236 / NHLBI NIH HHS N01HC95168 / NHLBI NIH HHS UL1 TR000040 / NCATS NIH HHS N01HC95165 / NHLBI NIH HHS P30 DK063491 / NIDDK NIH HHS N01HC95162 / NHLBI NIH HHS UL1 TR001420 / NCATS NIH HHS N01HC95161 / NHLBI NIH HHS N01 HC095168 / NHLBI NIH HHS N01HC95164 / NHLBI NIH HHS N01 HC095165 / NHLBI NIH HHS N01 HC095162 / NHLBI NIH HHS N01HC65237 / NHLBI NIH HHS N01HC95167 / NHLBI NIH HHS R01 HL111089 / NHLBI NIH HHS R01 HL092217 / NHLBI NIH HHS R01 HL124935 / NHLBI NIH HHS N02HL64278 / NHLBI NIH HHS HHSN268201300005C / NHLBI NIH HHS N01 HC065237 / NHLBI NIH HHS N01HC95159 / NHLBI NIH HHS HHSN268201600002C / NHLBI NIH HHS UL1 TR001079 / NCATS NIH HHS UL1 TR000124 / NCATS NIH HHS P30 DK020595 / NIDDK NIH HHS N01 HC065234 / NHLBI NIH HHS N01 HC065235 / NHLBI NIH HHS N01 HC095164 / NHLBI NIH HHS S10 OD020069 / NIH HHS K23 HL136853 / NHLBI NIH HHS R01 HL102830 / NHLBI NIH HHS N01HC65234 / NHLBI NIH HHS N01HC95160 / NHLBI NIH HHS U01 DK085501 / NIDDK NIH HHS R01 HL116747 / NHLBI NIH HHS HHSN268201600004C / NHLBI NIH HHS P60 DK020595 / NIDDK NIH HHS N01 HC095161 / NHLBI NIH HHS N01 HC095167 / NHLBI NIH HHS
- Language
- English
- Date published
- 2019
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology
- Record Identifier
- 9984214681902771
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