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Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.
Tuesday,2013-10-01 09:32 America/Los_Angeles — poolea2
| Title | Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Butler, AM, Yin, X, Evans, DS, Nalls, MA, Smith, EN, Tanaka, T, Li, G, Buxbaum, SG, Whitsel, EA, Alonso, A, Arking, DE, Benjamin, EJ, Berenson, GS, Bis, JC, Chen, W, Deo, R, Ellinor, PT, Heckbert, SR, Heiss, G, Hsueh, W-C, Keating, BJ, Kerr, KF, Li, Y, Limacher, MC, Liu, Y, Lubitz, SA, Marciante, KD, Mehra, R, Meng, YA, Newman, AB, Newton-Cheh, C, North, KE, Palmer, CD, Psaty, BM, P Quibrera, M, Redline, S, Reiner, AP, Rotter, JI, Schnabel, RB, Schork, NJ, Singleton, AB, J Smith, G, Soliman, EZ, Srinivasan, SR, Zhang, Z-M, Zonderman, AB, Ferrucci, L, Murray, SS, Evans, MK, Sotoodehnia, N, Magnani, JW, Avery, CL |
| Journal | Circ Cardiovasc Genet |
| Volume | 5 |
| Issue | 6 |
| Pagination | 639-46 |
| Date Published | 2012 Dec |
| ISSN | 1942-3268 |
| Keywords | Adult, African Americans, Cohort Studies, Electrocardiography, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide |
| Abstract | <p><b>BACKGROUND: </b>The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.</p><p><b>METHODS AND RESULTS: </b>We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 × 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 × 10(-8)).</p><p><b>CONCLUSIONS: </b>This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.</p> |
| DOI | 10.1161/CIRCGENETICS.112.963991 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 23139255 |
| PubMed Central ID | PMC3560365 |
| Grant List | HC-85083 / HC / NHLBI NIH HHS / United States M01-RR00425 / RR / NCRR NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States ZIA AG000513-11 / / Intramural NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N01 WH032112 / WH / WHI NIH HHS / United States N01 WH042122 / WH / WHI NIH HHS / United States R00 HL098458 / HL / NHLBI NIH HHS / United States HHSN268201100009I / HL / NHLBI NIH HHS / United States CA009330 / CA / NCI NIH HHS / United States HC-85082 / HC / NHLBI NIH HHS / United States N01-HC-95162 / HC / NHLBI NIH HHS / United States N01 WH044221 / WH / WHI NIH HHS / United States N01 WH32115 / WH / WHI NIH HHS / United States N01 WH032101 / WH / WHI NIH HHS / United States R01 HL075366 / HL / NHLBI NIH HHS / United States R21 DA027021 / DA / NIDA NIH HHS / United States HG006703 / HG / NHGRI NIH HHS / United States N01 WH042110 / WH / WHI NIH HHS / United States R01 HG006292 / HG / NHGRI NIH HHS / United States N01 HC095170 / HC / 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 R01 HL046380 / HL / NHLBI NIH HHS / United States K24 HL105780 / HL / NHLBI NIH HHS / United States N01 WH042114 / WH / WHI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States R01 HG006703 / HG / NHGRI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States N01 HC095167 / HC / NHLBI NIH HHS / United States N01 WH032105 / WH / WHI 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 N01 WH042107 / WH / WHI NIH HHS / United States 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