Association of lipid-related genetic variants with the incidence of atrial fibrillation: The AFGen consortium

Faye L. Norby, Samuel Adamsson Eryd, Maartje N. Niemeijer, Lynda M. Rose, Albert V. Smith, Xiaoyan Yin, Sunil K. Agarwal, Dan E. Arking, Daniel L. Chasman, Lin Y. Chen, Mark Eijgelsheim, Gunnar Engström, Oscar H. Franco, Jan Heeringa, George Hindy, Albert Hofman, Pamela L. Lutsey, Jared W. Magnani, David D. McManus, Marju Orho-MelanderJames S. Pankow, Gull Rukh, Christina Alexandra Schulz, André G. Uitterlinden, Christine M. Albert, Emelia J. Benjamin, Vilmundur Gudnason, J. Gustav Smith, Bruno H.C. Stricker, Alvaro Alonso

Research output: Contribution to journalArticle

Abstract

Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04). Conclusions In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.

Original languageEnglish (US)
Article numbere0151932
JournalPloS one
Volume11
Issue number3
DOIs
StatePublished - Mar 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Norby, F. L., Eryd, S. A., Niemeijer, M. N., Rose, L. M., Smith, A. V., Yin, X., Agarwal, S. K., Arking, D. E., Chasman, D. L., Chen, L. Y., Eijgelsheim, M., Engström, G., Franco, O. H., Heeringa, J., Hindy, G., Hofman, A., Lutsey, P. L., Magnani, J. W., McManus, D. D., ... Alonso, A. (2016). Association of lipid-related genetic variants with the incidence of atrial fibrillation: The AFGen consortium. PloS one, 11(3), [e0151932]. https://doi.org/10.1371/journal.pone.0151932