You are here
Impact of ancestry and common genetic variants on QT interval in African Americans.
Thursday,2013-12-19 17:06 America/Los_Angeles — poolea2
| Title | Impact of ancestry and common genetic variants on QT interval in African Americans. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | J Smith, G, Avery, CL, Evans, DS, Nalls, MA, Meng, YA, Smith, EN, Palmer, C, Tanaka, T, Mehra, R, Butler, AM, Young, T, Buxbaum, SG, Kerr, KF, Berenson, GS, Schnabel, RB, Li, G, Ellinor, PT, Magnani, JW, Chen, W, Bis, JC, J Curb, D, Hsueh, W-C, Rotter, JI, Liu, Y, Newman, AB, Limacher, MC, North, KE, Reiner, AP, P Quibrera, M, Schork, NJ, Singleton, AB, Psaty, BM, Soliman, EZ, Solomon, AJ, Srinivasan, SR, Alonso, A, Wallace, R, Redline, S, Zhang, Z-M, Post, WS, Zonderman, AB, Taylor, HA, Murray, SS, Ferrucci, L, Arking, DE, Evans, MK, Fox, ER, Sotoodehnia, N, Heckbert, SR, Whitsel, EA, Newton-Cheh, C |
| Corporate/Institutional Authors | CARe and COGENT consortia |
| Journal | Circ Cardiovasc Genet |
| Volume | 5 |
| Issue | 6 |
| Pagination | 647-55 |
| Date Published | 2012 Dec |
| ISSN | 1942-3268 |
| Keywords | Adult, African Americans, Aged, Electrocardiography, European Continental Ancestry Group, Female, Genealogy and Heraldry, Genetic Variation, Genome, Human, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide |
| Abstract | <p><b>BACKGROUND: </b>Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval.</p><p><b>METHODS AND RESULTS: </b>First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN.</p><p><b>CONCLUSIONS: </b>We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.</p> |
| DOI | 10.1161/CIRCGENETICS.112.962787 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 23166209 |
| PubMed Central ID | PMC3568265 |
| Grant List | M01-RR00425 / RR / NCRR NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States R00 HL098458 / HL / NHLBI NIH HHS / United States HHSN268201100009I / HL / NHLBI NIH HHS / United States N01-HC-95162 / HC / NHLBI NIH HHS / United States R01 HL075366 / HL / NHLBI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States R03 HD062783 / HD / NICHD NIH HHS / United States N01WH42129-32 / WH / WHI NIH HHS / United States 1-R01-ES017794 / ES / NIEHS NIH HHS / United States R01 HL046380 / HL / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States M01RR00080 / RR / NCRR NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States HL085251 / HL / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States HHSN268201100005C / / PHS HHS / United States R01 ES017794 / ES / NIEHS NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01-HC-95163 / HC / NHLBI NIH HHS / United States T32 CA009330 / CA / NCI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States N01-HC-95168 / HC / NHLBI NIH HHS / United States N01WH32100-2 / WH / WHI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States HHSN268201100009C / / PHS HHS / United States HHSN268201100011I / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01-HL-111089 / HL / NHLBI NIH HHS / United States N01-HC-95159 / HC / NHLBI NIH HHS / United States N01WH32108-9 / WH / WHI NIH HHS / United States UL1 RR025774 / RR / NCRR NIH HHS / United States 1R01AG032098-01A1 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01-WH-2-2110 / WH / WHI NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States N01-HC-95165 / HC / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States R01 HL098283 / HL / NHLBI NIH HHS / United States R01 AG016592 / AG / NIA NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N02HL64278 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States N01WH42107-26 / WH / WHI NIH HHS / United States HHSN268201100010C / / PHS HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States P30 AG028740 / AG / NIA NIH HHS / United States HL 46380 / HL / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01HC95170 / HL / NHLBI NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States HL075366 / HL / NHLBI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States / / Intramural NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States HHSN268201100008C / / PHS HHS / United States P20 MD006899 / MD / NIMHD NIH HHS / United States HHSN268201100012C / / PHS HHS / United States N01-HC-95169 / HC / NHLBI NIH HHS / United States N01WH32122 / WH / WHI NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States 5T32CA009330-30 / CA / NCI NIH HHS / United States N01-HC-95164 / HC / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States R01-HL-071205 / HL / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01-HC-95160 / HC / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268201100007C / / PHS HHS / United States N01-HC-95171 / HC / NHLBI NIH HHS / United States N01WH32105-6 / WH / WHI NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States N01WH32111-13 / WH / WHI NIH HHS / United States HD-062783 / HD / NICHD NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01WH32118-32119 / WH / WHI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States R01-HL-088456 / HL / NHLBI NIH HHS / United States N01-HC-95172 / HC / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States HHSN268201100011C / / PHS HHS / United States AG-16592 / AG / NIA NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States N01HC95171 / HL / NHLBI NIH HHS / United States R01 HL071205 / HL / NHLBI NIH HHS / United States Z01 AG000513 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-95161 / HC / NHLBI NIH HHS / United States HHSN268200782096C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States R03 HD061437 / HD / NICHD NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States HHSN268201100006C / / PHS HHS / United States N01-HC-95166 / HC / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States 1R01HL098283 / HL / NHLBI NIH HHS / United States HD-061437 / HD / NICHD NIH HHS / United States L30 HL082455 / HL / NHLBI NIH HHS / United States R00-HL-098458 / HL / NHLBI NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States M01 RR000080 / RR / NCRR NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01WH32115 / WH / WHI NIH HHS / United States N01-HC-95170 / HC / NHLBI NIH HHS / United States N01WH44221 / WH / WHI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States K23 HL080025 / HL / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States R01 HL111089 / HL / NHLBI NIH HHS / United States N01WH24152 / WH / WHI NIH HHS / United States N01-HC-95167 / HC / NHLBI NIH HHS / United States N01-HC-65226 / HC / NHLBI NIH HHS / United States N01HC95172 / HL / NHLBI NIH HHS / United States |