title: Genetic Investigation Into the Differential Risk of Atrial Fibrillation Among Black and White Individuals.
abstract: White persons have a higher risk of atrial fibrillation (AF) compared with black individuals despite a lower prevalence of risk factors. This difference may be due, at least in part, to genetic factors.
  
  
  
  To determine whether 9 single-nucleotide polymorphisms (SNPs) associated with AF account for this paradoxical differential racial risk for AF and to use admixture mapping to search genome-wide for loci that may account for this phenomenon.
  
  
  
  Genome-wide admixture analysis and candidate SNP study involving 3 population-based cohort studies that were initiated between 1987 and 1997, including the Cardiovascular Health Study (CHS) (n = 4173), the Atherosclerosis Risk in Communities (ARIC) (n = 12 341) study, and the Health, Aging, and Body Composition (Health ABC) (n = 1015) study. In all 3 studies, race was self-identified. Cox proportional hazards regression models and the proportion of treatment effect method were used to determine the impact of 9 AF-risk SNPs among participants from CHS and the ARIC study. The present study began July 1, 2012, and was completed in 2015.
  
  
  
  Incident AF systematically ascertained using clinic visit electrocardiograms, hospital discharge diagnosis codes, death certificates, and Medicare claims data.
  
  
  
  A single SNP, rs10824026 (chromosome 10: position 73661450), was found to significantly mediate the higher risk for AF in white participants compared with black participants in CHS (11.4%; 95% CI, 2.9%-29.9%) and ARIC (31.7%; 95% CI, 16.0%-53.0%). Admixture mapping was performed in a meta-analysis of black participants within CHS (n = 811), ARIC (n = 3112), and Health ABC (n = 1015). No loci that reached the prespecified statistical threshold for genome-wide significance were identified.
  
  
  
  The rs10824026 SNP on chromosome 10q22 mediates a modest proportion of the increased risk of AF among white individuals compared with black individuals, potentially through an effect on gene expression levels of MYOZ1. No additional genetic variants accounting for a significant portion of the differential racial risk of AF were identified with genome-wide admixture mapping, suggesting that additional genetic or environmental influences beyond single SNPs in isolation may account for the paradoxical racial risk of AF among white individuals and black individuals.
authors.affiliation: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Roberts
authors.affiliation: Institute of Human Genetics and Department of Medicine, University of California, San Francisco.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, University of Washington, Seattle.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Dewland
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco.
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.affiliation: Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, University of Washington, Seattle7Cardiovascular Health Research Unit, University of Washington, Seattle8Departments of Medicine and Health Services, University of Washington, Seattle9Group Health Research Institute, Group Heal.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Olgin
authors.affiliation: Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.affiliation: Institute of Human Genetics and Department of Medicine, University of California, San Francisco.
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: Department of Medicine, University of California, San Francisco 12Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.affiliation: Department of Medicine, University of California, San Francisco.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bibbins-Domingo
authors.affiliation: Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland.
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Marco V
authors.initials: MV
authors.lastname: Perez
authors.affiliation: Institute of Human Genetics and Department of Medicine, University of California, San Francisco.
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.affiliation: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Marcus
mesh_terms: D050197:Atherosclerosis; D001281:Atrial Fibrillation / Q000208:ethnology / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D009124:Muscle Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C419780:MYOZ1 protein, human; D009124:Muscle Proteins