Why the study?
Do lipid-specific gene scores, acting as instrumental variables for blood lipid levels, affect the incidence of atrial fibrillation in individuals of European ancestry?
Meta-Analysis (n=64,901)
Yes
Do lipid-specific gene scores, acting as instrumental variables for blood lipid levels, affect the incidence of atrial fibrillation in individuals of European ancestry?
Hazard Ratio: 1.01 (95% CI 0.98–1.03)
Genetically determined lipid levels were not associated with incident atrial fibrillation, suggesting that previously observed observational associations between blood lipids and AF risk may not be causal.
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.
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Norby et al. (2016) conducted a meta-analysis in Atrial Fibrillation (n=64,901). Lipid-related genetic variants (lipid gene scores) vs. Per 1-standard deviation increase in lipid gene score was evaluated on Incidence of Atrial Fibrillation (HDLc gene score) (HR 1.01, 95% CI 0.98-1.03).
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