GWAS of QRS Duration Identifies New Loci Specific to Hispanic/Latino Populations

Swenson, B.; Louie, T.; Lin, H. J.; Mendez-Gairldez, R.; Below, J. E.; Laurie, C. C.; Kerr, K. F.; Highland, H.; Thornton, T. A.; Ryckman, K. K.; Kooperberg, C.; Soliman, E. Z.; Seyerle, A. A.; Guo, X.; Taylor, K. D.; Yao, J.; Heckbert, S. R.; Darbar, D.; Petty, L. E.; McKnight, B.; Cheng, S.; Bello, N. A.; Whitsel, E. A.; Hanis, C. L.; Nalls, M. A.; Evans, D. S.; Rotter, J. I.; Sofer, T.; Avery, C.; Sotoodehnia, N.

doi:10.1101/363457

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bioRxiv · 10.1101/363457

GWAS of QRS Duration Identifies New Loci Specific to Hispanic/Latino Populations

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Abstract

BackgroundThe 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.\n\nMethodsWe 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.\n\nResultsWe 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.\n\nConclusionsOur 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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Swenson, B., Louie, T., Lin, H. J., Mendez-Gairldez, R., Below, J. E., Laurie, C. C., Kerr, K. F., Highland, H., Thornton, T. A., Ryckman, K. K., Kooperberg, C., Soliman, E. Z., Seyerle, A. A., Guo, X., Taylor, K. D., Yao, J., Heckbert, S. R., Darbar, D., Petty, L. E., McKnight, B., Cheng, S., Bello, N. A., Whitsel, E. A., Hanis, C. L., Nalls, M. A., Evans, D. S., Rotter, J. I., Sofer, T., Avery, C., Sotoodehnia, N.. 2018-07-06. GWAS of QRS Duration Identifies New Loci Specific to Hispanic/Latino Populations. https://doi.org/10.1101/363457

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