title: Large-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) project.
abstract: BACKGROUND
  The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.
  
  
  RESULTS
  We examined a panel of approximately 50,000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18,524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72-1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16-1.69; P=0.0005).
  
  
  CONCLUSIONS
  In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA. schnabelr@gmx.de
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lubitz
authors.forename: Ermeg L
authors.initials: EL
authors.lastname: Alkylbekova
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Marcus
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Sinner
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Rajat
authors.initials: R
authors.lastname: Deo
authors.forename: Donald M
authors.initials: DM
authors.lastname: Lloyd-Jones
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.forename: Reena
authors.initials: R
authors.lastname: Mehra
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Ervin R
authors.initials: ER
authors.lastname: Fox
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Martina
authors.initials: M
authors.lastname: Müller-Nurasyid
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Young
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Farlow
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodehnia
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Stefan
authors.initials: S
authors.lastname: Kääb
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000483:Alleles; D001281:Atrial Fibrillation / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054555:National Heart, Lung, and Blood Institute (U.S.); D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D019947:Receptors, Interleukin-6