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

TitleAssociation of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium.
Publication TypeJournal Article
Year of Publication2016
AuthorsNorby FL, Eryd SAdamsson, Niemeijer MN, Rose LM, Smith AV, Yin X, Agarwal SK, Arking DE, Chasman DL, Chen LYee, Eijgelsheim M, Engström G, Franco OH, Heeringa J, Hindy G, Hofman A, Lutsey PL, Magnani JW, McManus DD, Orho-Melander M, Pankow JS, Rukh G, Schulz C-A, Uitterlinden AG, Albert CM, Benjamin EJ, Gudnason V, J Smith G, Stricker BHC
Secondary AuthorsAlonso A
JournalPLoS One
Volume11
Issue3
Paginatione0151932
Date Published2016
ISSN1932-6203
KeywordsAged, Atrial Fibrillation, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Confidence Intervals, Female, Genetic Association Studies, Genetic Pleiotropy, Genetic Predisposition to Disease, Genetic Variation, Humans, Lipids, Male, Meta-Analysis as Topic, Middle Aged, Multivariate Analysis
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.

DOI10.1371/journal.pone.0151932
Alternate JournalPLoS One
PubMed ID26999784
PubMed Central IDPMC4801208
Grant ListHL099355 / HL / NHLBI NIH HHS / United States
09SDG2280087 / / PHS HHS / United States
16EIA26410001 / AHA / American Heart Association-American Stroke Association / United States
UL1 TR001453 / TR / NCATS NIH HHS / United States
R01 HL116690 / HL / NHLBI NIH HHS / United States
6R01-NS 17950 / NS / NINDS NIH HHS / United States
N01-AG-12100 / AG / NIA NIH HHS / United States
HL 69757 / HL / NHLBI NIH HHS / United States
RC1HL 099452 / HL / NHLBI NIH HHS / United States
1R01 AG028321 / AG / NIA NIH HHS / United States
HL 043851 / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
KL2RR031981 / RR / NCRR NIH HHS / United States
HL-093613 / HL / NHLBI NIH HHS / United States
1R01 HL076784 / HL / NHLBI NIH HHS / United States
RC1HL101056 / HL / NHLBI NIH HHS / United States
CA 047988 / CA / NCI NIH HHS / United States
2R01 HL092577 / HL / NHLBI NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States