title: Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study.
abstract: BACKGROUND
  Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited.
  
  
  METHODS
  We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987-1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates.
  
  
  RESULTS
  During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12-1.32) for glycolithocholate sulfate and 1.22 (1.10-1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes.
  
  
  CONCLUSIONS
  We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted.
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
authors.affiliation: Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Division of Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Waqas T
authors.initials: WT
authors.lastname: Qureshi
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Grams
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.|Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.|Department of Medicine-Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Loehr
authors.affiliation: 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: Mount Sinai Heart Hospital, New York, New York, United States of America.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Agarwal
authors.affiliation: Metabolon, Inc., Durham, North Carolina, United States of America.
authors.forename: Danny
authors.initials: D
authors.lastname: Alexander
authors.affiliation: Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D001741:Black or African American / Q000706:statistics & numerical data*; D050197:Atherosclerosis / Q000453:epidemiology*; D001281:Atrial Fibrillation / Q000097:blood / Q000453:epidemiology* / Q000208:ethnology / Q000378:metabolism*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D012111:Residence Characteristics / Q000706:statistics & numerical data*