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

TitleGWAS of QRS duration identifies new loci specific to Hispanic/Latino populations.
Publication TypePublication
Year2019
AuthorsSwenson BR, Louie T, Lin HJ, Méndez-Giráldez R, Below JE, Laurie CC, Kerr KF, Highland H, Thornton TA, Ryckman KK, Kooperberg C, Soliman EZ, Seyerle AA, Guo X, Taylor KD, Yao J, Heckbert SR, Darbar D, Petty LE, McKnight B, Cheng S, Bello NA, Whitsel EA, Hanis CL, Nalls MA, Evans DS, Rotter JI, Sofer T, Avery CL, Sotoodehnia N
JournalPLoS One
Volume14
Issue6
Paginatione0217796
Date Published2019
ISSN1932-6203
KeywordsElectrocardiography, Genetic Loci, genome-wide association study, Hispanic Americans, Humans, Middle Aged, Molecular Sequence Annotation, Phenotype, Polymorphism, Single Nucleotide
Abstract

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 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.

DOI10.1371/journal.pone.0217796
Alternate JournalPLoS One
PubMed ID31251759
PubMed Central IDPMC6599128
Grant ListN01HC95160 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
N01 HC095164 / HC / NHLBI NIH HHS / United States
U01 DK085501 / DK / NIDDK NIH HHS / United States
N01 HC095163 / HC / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
R01 HL092217 / HL / NHLBI NIH HHS / United States
N01 HC065234 / HC / NHLBI NIH HHS / United States
HHSN268201600002C / HL / NHLBI NIH HHS / United States
N01 HC095168 / HC / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
R01 HL124935 / HL / NHLBI NIH HHS / United States
HHSN268201600018C / HL / NHLBI NIH HHS / United States
R01 HL142302 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01 HC095162 / HC / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
N01 HC095165 / HC / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01 HC065237 / HC / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
R01 HL102830 / HL / NHLBI NIH HHS / United States
R01 DK073541 / DK / NIDDK NIH HHS / United States
N01 HC095169 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
T32 HL007779 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
HHSN268201600003C / HL / NHLBI NIH HHS / United States
N01 HC065233 / HC / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
HHSN268201300024C / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01 HC095161 / HC / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
T32 HL139439 / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
HHSN268201600004C / HL / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
HHSN268201600001C / HL / NHLBI NIH HHS / United States
N01 HC065236 / HC / NHLBI NIH HHS / United States
R01 AI085014 / AI / NIAID NIH HHS / United States
N01 HC095166 / HC / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
T32 HL007374 / HL / NHLBI NIH HHS / United States
K23 HL136853 / HL / NHLBI NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01 HC095167 / HC / NHLBI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
N01 HC065235 / HC / NHLBI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
P60 DK020595 / DK / NIDDK NIH HHS / United States
N01 HC095160 / HC / NHLBI NIH HHS / United States
MS#: 
0361
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
ECI: 
Yes
Manuscript Status: 
Published