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Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval.
Wednesday,2015-03-04 14:08 America/Los_Angeles — zdrager
| Title | Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Seyerle, AA, Young, AM, Jeff, JM, Melton, PE, Jorgensen, NW, Lin, Y, Carty, CL, Deelman, E, Heckbert, SR, Hindorff, LA, Jackson, RD, Martin, LW, Okin, PM, Perez, MV, Psaty, BM, Soliman, EZ, Whitsel, EA, North, KE, Laston, S, Kooperberg, C, Avery, CL |
| Journal | Epidemiology |
| Volume | 25 |
| Issue | 6 |
| Pagination | 790-8 |
| Date Published | 2014 Nov |
| ISSN | 1531-5487 |
| Keywords | Aged, Continental Population Groups, Electrocardiography, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Long QT Syndrome, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Risk Factors |
| Abstract | <p><b>BACKGROUND: </b>QT interval (QT) prolongation is an established risk factor for ventricular tachyarrhythmia and sudden cardiac death. Previous genome-wide association studies in populations of the European descent have identified multiple genetic loci that influence QT, but few have examined these loci in ethnically diverse populations.</p><p><b>METHODS: </b>Here, we examine the direction, magnitude, and precision of effect sizes for 21 previously reported SNPs from 12 QT loci, in populations of European (n = 16,398), African (n = 5,437), American Indian (n = 5,032), Hispanic (n = 1,143), and Asian (n = 932) descent as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. Estimates obtained from linear regression models stratified by race/ethnicity were combined using inverse-variance weighted meta-analysis. Heterogeneity was evaluated using Cochran's Q test.</p><p><b>RESULTS: </b>Of 21 SNPs, 7 showed consistent direction of effect across all 5 populations, and an additional 9 had estimated effects that were consistent across 4 populations. Despite consistent direction of effect, 9 of 16 SNPs had evidence (P < 0.05) of heterogeneity by race/ethnicity. For these 9 SNPs, linkage disequilibrium plots often indicated substantial variation in linkage disequilibrium patterns among the various racial/ethnic groups, as well as possible allelic heterogeneity.</p><p><b>CONCLUSIONS: </b>These results emphasize the importance of analyzing racial/ethnic groups separately in genetic studies. Furthermore, they underscore the possible utility of trans-ethnic studies to pinpoint underlying casual variants influencing heritable traits such as QT.</p> |
| DOI | 10.1097/EDE.0000000000000168 |
| Alternate Journal | Epidemiology |
| PubMed ID | 25166880 |
| PubMed Central ID | PMC4380285 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States N01 WH042122 / WH / WHI NIH HHS / United States UL1 RR033176 / RR / NCRR NIH HHS / United States R00 HL098458 / HL / NHLBI NIH HHS / United States N01WH32100 / WH / WHI NIH HHS / United States 32105-6 / / PHS HHS / United States UL1RR033176 / RR / NCRR NIH HHS / United States N01 WH32115 / WH / WHI NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States U01 HG007419 / HG / NHGRI NIH HHS / United States N01 WH042110 / WH / WHI NIH HHS / United States U01 HL041642 / HL / NHLBI NIH HHS / United States L30 HL109408 / HL / NHLBI NIH HHS / United States U01 HL65520 / HL / NHLBI NIH HHS / United States N01HV48195 / HL / NHLBI NIH HHS / United States N01WH44221 / WH / WHI NIH HHS / United States N01-HV-48195 / HV / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01 WH042114 / WH / WHI NIH HHS / United States U01 HL041654 / HL / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01 WH032105 / WH / WHI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States U01 HL65521 / HL / NHLBI NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States N01 WH042107 / WH / WHI NIH HHS / United States N01 WH042126 / WH / WHI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States U01 HG004802 / HG / NHGRI NIH HHS / United States U01 HG007416 / HG / NHGRI NIH HHS / United States U01 HL41642 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01 WH042108-011 / WH / WHI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States K99 HL098458 / HL / NHLBI NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States 42107-26 / / PHS HHS / United States 32115 / / PHS HHS / United States N01 WH022110 / WH / WHI NIH HHS / United States N01 WH042121 / WH / WHI NIH HHS / United States N01 WH032111 / WH / WHI NIH HHS / United States N01 WH032122 / WH / WHI NIH HHS / United States N01 WH032118 / WH / WHI NIH HHS / United States N01 WH042130 / WH / WHI NIH HHS / United States N01 WH042115 / WH / WHI NIH HHS / United States U01HG004803 / HG / NHGRI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01 WH042113 / WH / WHI NIH HHS / United States N01 WH042131 / WH / WHI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 WH042119 / WH / WHI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States U01 HL041652 / HL / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01 WH042116 / WH / WHI NIH HHS / United States 32100-2 / / PHS HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 24152 / / PHS HHS / United States U01 HL41654 / HL / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01 WH042117 / WH / WHI NIH HHS / United States 42129-32 / / PHS HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States T32 HL007824 / HL / NHLBI NIH HHS / United States N01 WH042109 / WH / WHI NIH HHS / United States U01 HL41652 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01 WH42124 / OD / NIH HHS / United States U01 HG004803 / HG / NHGRI NIH HHS / United States 32118-32119 / / PHS HHS / United States N01 WH042132 / WH / WHI NIH HHS / United States U01HG004798-01 / HG / NHGRI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States 32108-9 / / PHS HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01 HC055015 / HC / NHLBI NIH HHS / United States HHSN268200800007C / / PHS HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01 WH042112 / WH / WHI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01 WH042125 / WH / WHI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01WH42118 / WH / WHI NIH HHS / United States U01 HL065521 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01 WH042111 / WH / WHI NIH HHS / United States HHSN268201200036C / / PHS HHS / United States U01HG004790 / HG / NHGRI NIH HHS / United States U01 HG004798 / HG / NHGRI NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States 32122 / / PHS HHS / United States U01HG004801-01 / HG / NHGRI NIH HHS / United States N01 WH022110-024 / WH / WHI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 WH042120 / WH / WHI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States N01 WH032108 / WH / WHI NIH HHS / United States 44221 / / PHS HHS / United States T32 HL007055 / HL / NHLBI NIH HHS / United States R01 HL109301 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States 32111-13 / / PHS HHS / United States AG023629 / AG / NIA NIH HHS / United States N01 WH042123 / WH / WHI NIH HHS / United States N01 WH032119 / WH / WHI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States N01 WH042129 / WH / WHI NIH HHS / United States U01 HL065520 / HL / NHLBI NIH HHS / United States N01 WH024152 / WH / WHI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01 HC55222 / HC / NHLBI NIH HHS / United States U01 HG004801 / HG / NHGRI NIH HHS / United States |