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| Keywords | |
| Abstract |
<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| Year of Publication |
2019
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| Journal |
PLoS One
|
| Volume |
14
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| Issue |
6
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| Number of Pages |
e0217796
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| Date Published |
2019
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| ISSN Number |
1932-6203
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| DOI |
10.1371/journal.pone.0217796
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| Alternate Journal |
PLoS One
|
| PMID |
31251759
|
| Download citation |