GWAS of QRS Duration Identifies New Loci Specific to Hispanic/Latino Populations
By
Brenton R. Swenson,
Tin Louie,
Henry J Lin,
Raú MéndezGiráldez,
Jennifer E Below,
Cathy C Laurie,
Kathleen F Kerr,
Heather Highland,
Timothy A. Thornton,
Kelli K Ryckman,
Charles Kooperberg,
Elsayed Z. Soliman,
Amanda A. Seyerle,
Xiuqing Guo,
Kent D. Taylor,
Jie Yao,
Susan R. Heckbert,
Dawood Darbar,
Lauren E Petty,
Barbara McKnight,
Susan Cheng,
Natalie A Bello,
Eric A. Whitsel,
Craig L Hanis,
Mike A Nalls,
Daniel S Evans,
Jerome I. Rotter,
Tamar Sofer,
Christy Avery,
Nona Sotoodehnia
Posted 06 Jul 2018
bioRxiv DOI: 10.1101/363457
(published DOI: 10.1371/journal.pone.0217796)
Background. 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 association 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 for intronic SNP rs3922344 (P= 8.56x10-26) in SCN5A/SCN10A. Three additional 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.
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