title: Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium.
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.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Faye L
authors.initials: FL
authors.lastname: Norby
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Samuel Adamsson
authors.initials: SA
authors.lastname: Eryd
authors.affiliation: Department of Epidemiology, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.
authors.forename: Maartje N
authors.initials: MN
authors.lastname: Niemeijer
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Rose
authors.affiliation: Icelandic Heart Association, Research Institute, Kopavogur, Iceland.|The University of Iceland, Reykjavik, Iceland.
authors.forename: Albert V
authors.initials: AV
authors.lastname: Smith
authors.affiliation: Cardiology and Preventive Medicine Sections, Department of Biostatistics, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.affiliation: Icahn School of Medicine, Mount Sinai Heart Center, New York, New York, United States of America.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Agarwal
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Chasman
authors.affiliation: Cardiac Arrhythmia Center, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
authors.forename: Lin Y
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Eijgelsheim
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.affiliation: Department of Epidemiology, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Epidemiology, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Heeringa
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: George
authors.initials: G
authors.lastname: Hindy
authors.affiliation: Department of Epidemiology, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Lutsey
authors.affiliation: Cardiology and Preventive Medicine Sections, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.|The National Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts, United States of America.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.affiliation: Departments of Medicine and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: David D
authors.initials: DD
authors.lastname: McManus
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Gull
authors.initials: G
authors.lastname: Rukh
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Christina-Alexandra
authors.initials: CA
authors.lastname: Schulz
authors.affiliation: Department of Epidemiology, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Albert
authors.affiliation: Cardiology and Preventive Medicine Sections, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.|The National Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts, United States of America.|Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: Icelandic Heart Association, Research Institute, Kopavogur, Iceland.|The University of Iceland, Reykjavik, Iceland.
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.|Department of Cardiology, Lund University, Lund, Sweden.
authors.forename: J Gustav
authors.initials: JG
authors.lastname: Smith
authors.affiliation: Department of Epidemiology, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands.|Inspectorate of Health Care, Utrecht, the Netherlands.
authors.forename: Bruno H C
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D056726:Genetic Association Studies; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids