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GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations

dc.contributor.authorPetty, Lauren E.
dc.contributor.authorBelow, Jennifer E.
dc.identifier.citationSwenson BR, Louie T, Lin HJ, Me´ndez- Gira´ldez R, Below JE, Laurie CC, et al. (2019) GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations. PLoS ONE 14(6): e0217796. pone.0217796en_US
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at
dc.description.abstractBackground 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. Methods 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. Results 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. Conclusions 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.en_US
dc.description.sponsorshipJEB is supported by NIH (R01HL142302). AAS is supported by NHLBI training grants (T32HL7055 and T32HL07779). DD is supported by NIH (R01HL124935; T32 HL139439) and NHLBI (HL092217). NAB is supported by NIH/NHLBI K23 HL136853 and the Katz Foundation. CLA is supported by NIH (T32HL007055). NS is supported by the NIH (HL116747, HL111089); and the Laughlin family. Additionally this work is indirectly supported by the funding received by each cohort study which contributed data to the analysis: Hispanic Community Health Study/Study of Latinos (HCHS/SOL): The baseline examination of HCHS/SOL was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), San Diego State University (N01-HC65237), and the Brigham and Women's Hospital (HHSN268201300024C). The following Institutes/Centers/Offices contributed to the first phase of HCHS/SOL through a transfer of funds to the National Hearth Lung and Blood Institute (NHLBI): National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. The Genetic Analysis Center at University of Washington was supported by NHLBI and National Institute of Dental and Craniofacial Research contracts (HHSN268 201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000124, and NIDDK Diabetes Research Center (DRC) grant DK063491. Multi-Ethnic Study of Atherosclerosis (MESA): MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Starr County Study: This work was supported in part by grants DK073541, DK020595, AI085014, DK085501, and HL102830 from the National Institutes of Health and funds from the University of Texas Health Science Center at Houston. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health (NIH) to The Johns Hopkins University, contract number HHSN26820078209 6C. Women's Health Initiative: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts: HHSN268201600018C, HHSN26820 1600001C, HHSN268201600002C, HHSN2682 01600003C, and HHSN268201600004C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.publisherPLoS Oneen_US
dc.rightsCopyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
dc.titleGWAS of QRS duration identifies new loci specific to Hispanic/Latino populationsen_US

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