Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium

• Published in: PloS one 2016-03, Vol.11 (3), p.e0151932-e0151932
• Main Authors: Norby, Faye L, Eryd, Samuel Adamsson, Niemeijer, Maartje N, Rose, Lynda M, Smith, Albert V, Yin, Xiaoyan, Agarwal, Sunil K, Arking, Dan E, Chasman, Daniel L, Chen, Lin Y, Eijgelsheim, Mark, Engström, Gunnar, Franco, Oscar H, Heeringa, Jan, Hindy, George, Hofman, Albert, Lutsey, Pamela L, Magnani, Jared W, McManus, David D, Orho-Melander, Marju, Pankow, James S, Rukh, Gull, Schulz, Christina-Alexandra, Uitterlinden, André G, Albert, Christine M, Benjamin, Emelia J, Gudnason, Vilmundur, Smith, J Gustav, Stricker, Bruno H C, Alonso, Alvaro
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Atrial fibrillation; Atrial Fibrillation - blood; Atrial Fibrillation - genetics; Biology and Life Sciences; Blood; Blood lipids; Cardiac arrhythmia; Cholesterol; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Clinical Medicine; Cohort Studies; Confidence Intervals; Consortia; Female; Fibrillation; Genetic Association Studies; Genetic diversity; Genetic Pleiotropy; Genetic Predisposition to Disease; Genetic variance; Genetic Variation; Health risk assessment; Humans; Incidence; Klinisk medicin; Lipids; Lipids - blood; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine and Health Sciences; Meta-Analysis as Topic; Middle Aged; Multivariate Analysis; Pleiotropy; Preventive medicine; Risk factors; Single-nucleotide polymorphism; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151932

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. 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. 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). In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.