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Genetic variants related to height and risk of atrial fibrillation: the cardiovascular health study.
Wednesday,2015-03-04 14:06 America/Los_Angeles — zdrager
| Title | Genetic variants related to height and risk of atrial fibrillation: the cardiovascular health study. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Rosenberg, MA, Kaplan, RC, Siscovick, DS, Psaty, BM, Heckbert, SR, Newton-Cheh, C, Mukamal, KJ |
| Journal | Am J Epidemiol |
| Volume | 180 |
| Issue | 2 |
| Pagination | 215-22 |
| Date Published | 2014 Jul 15 |
| ISSN | 1476-6256 |
| Keywords | African Americans, Aged, Atrial Fibrillation, Body Height, Endonucleases, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Longitudinal Studies, Male, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk Factors |
| Abstract | <p>Increased height is a known independent risk factor for atrial fibrillation (AF). However, whether genetic determinants of height influence risk is uncertain. In this candidate gene study, we examined the association of 209 height-associated single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of European descent from the Cardiovascular Health Study, a prospective cohort study of older adults (aged ≥ 65 years) enrolled in 1989-1990. After a median follow-up period of 13.2 years, 879 participants developed incident AF. The height-associated SNPs together explained approximately 10% of the variation in height (P = 6.0 × 10(-8)). Using an unweighted genetic height score, we found a nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95% confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that genetically predicted height was strongly associated with AF risk (per 10 cm, hazard ratio = 1.30, 95% confidence interval: 1.03, 1.64; P = 0.03). Importantly, for all models, the inclusion of actual height completely attenuated the genetic height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was independently associated with AF and may warrant future study. In conclusion, we found that genetic determinants of height appear to increase the risk of AF, primarily via height itself. This approach of examining SNPs associated with an intermediate phenotype should be considered as a method for identifying novel genetic targets.</p> |
| DOI | 10.1093/aje/kwu126 |
| Alternate Journal | Am. J. Epidemiol. |
| PubMed ID | 24944287 |
| PubMed Central ID | PMC4082343 |
| Grant List | N01HC55222 / HC / NHLBI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL068986 / HL / NHLBI NIH HHS / United States 1R01AG031890 / AG / NIA NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States HL068986 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States UL1 TR001073 / TR / NCATS NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States HHSN268200800007C / / PHS HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States HL103612 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States R01 AG031890 / AG / NIA NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States |