Genetic variants related to height and risk of atrial fibrillation

Michael A. Rosenberg, Robert C. Kaplan, David S. Siscovick, Bruce M. Psaty, Susan R. Heckbert, Christopher Newton-Cheh, Kenneth J. Mukamal

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalAmerican Journal of Epidemiology
Volume180
Issue number2
DOIs
StatePublished - Jul 15 2014
Externally publishedYes

Keywords

  • atrial fibrillation
  • cardiovascular disease
  • genetics
  • risk factors
  • risk prediction

ASJC Scopus subject areas

  • Epidemiology

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  • Cite this

    Rosenberg, M. A., Kaplan, R. C., Siscovick, D. S., Psaty, B. M., Heckbert, S. R., Newton-Cheh, C., & Mukamal, K. J. (2014). Genetic variants related to height and risk of atrial fibrillation. American Journal of Epidemiology, 180(2), 215-222. https://doi.org/10.1093/aje/kwu126