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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.

Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
TitleLarge-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.
Publication TypeJournal Article
Year of Publication2011
AuthorsSchnabel, RB, Kerr, KF, Lubitz, SA, Alkylbekova, EL, Marcus, GM, Sinner, MF, Magnani, JW, Wolf, PA, Deo, R, Lloyd-Jones, DM, Lunetta, KL, Mehra, R, Levy, D, Fox, ER, Arking, DE, Mosley, TH, Müller-Nurasyid, M, Young, TR, Wichmann, H-E, Seshadri, S, Farlow, DN, Rotter, JI, Soliman, EZ, Glazer, NL, Wilson, JG, Breteler, MMB, Sotoodehnia, N, Newton-Cheh, C, Kääb, S, Ellinor, PT, Alonso, A, Benjamin, EJ, Heckbert, SR
Corporate/Institutional AuthorsCandidate Gene Association Resource (CARe) Atrial Fibrillation/Electrocardiography Working Group,
JournalCirc Cardiovasc Genet
Volume4
Issue5
Pagination557-64
Date Published2011 Oct
ISSN1942-3268
KeywordsAfrican Americans, Aged, Alleles, Atrial Fibrillation, Chromosomes, Human, Pair 4, Cohort Studies, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Polymorphism, Single Nucleotide, Receptors, Interleukin-6, Risk Factors, Stroke, United States
Abstract<p><b>BACKGROUND: </b>The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.</p><p><b>METHODS AND RESULTS: </b>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).</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1161/CIRCGENETICS.110.959197
Alternate JournalCirc Cardiovasc Genet
PubMed ID21846873
PubMed Central IDPMC3224824
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
R01AG027002 / AG / NIA NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
T32 HL007575-26A1 / HL / NHLBI NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
R21 DA027021 / DA / NIDA NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
R01 HL059367-11 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
K24 HL105780 / HL / NHLBI NIH HHS / United States
RC1HL099452 / HL / NHLBI NIH HHS / United States
U01 HL080295-04 / HL / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
R01 HL087652-03 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
UL1 RR025005-05 / RR / NCRR NIH HHS / United States
R01-HL080295 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01HL093029 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
R01 HL104156 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268200900055C / / PHS HHS / United States
HHSN268200900055C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
M01 RR000069 / RR / NCRR NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 AG027002-06 / AG / NIA NIH HHS / United States
T32 HL007575 / HL / NHLBI NIH HHS / United States
N01 HC065226 / HC / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
P30 DK063491-03 / DK / NIDDK NIH HHS / United States
R01 HL086694-05 / HL / NHLBI NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
AG033193 / AG / NIA NIH HHS / United States
RC1 HL099452 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
R01 HL080295-07 / HL / NHLBI NIH HHS / United States
RC1 HL101056 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
R01 AG008122-20 / AG / NIA NIH HHS / United States
R01 HL092577-04 / HL / NHLBI NIH HHS / United States
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N01HC55015 / HL / NHLBI NIH HHS / United States
R01 HL093029 / HL / NHLBI NIH HHS / United States
NS17950 / NS / NINDS NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
AG028321 / AG / NIA NIH HHS / United States
M01 RR000069-46 / RR / NCRR NIH HHS / United States
RC1HL101056 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
HL105780 / HL / NHLBI NIH HHS / United States
AG08122 / AG / NIA NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
R21 DA027021-02S1 / DA / NIDA NIH HHS / United States
R01 NS017950-29 / NS / NINDS NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
R01 HL087641-03 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
RC1 HL099452-01 / RC / CCR NIH HHS / United States
R01 HL093029-02 / HL / NHLBI NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
L30 HL097675 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
N01-HC-55222 / HC / NHLBI NIH HHS / United States
M01RR00069 / RR / NCRR NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
DA027021 / DA / NIDA NIH HHS / United States
AG031287 / AG / NIA NIH HHS / United States
RC1 HL099452-01 / HL / NHLBI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
R01 AG027002 / AG / NIA NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
R01 HL104156-03 / HL / NHLBI NIH HHS / United States
U01 HG004402-02S1 / HG / NHGRI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
R01HL087652 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 AG031287-02 / AG / NIA NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
R01 AG028321-05 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
1R01HL092577 / HL / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 AG028321 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
RC1 HL101056-02 / HL / NHLBI NIH HHS / United States
R01 AG033193-03 / AG / NIA NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
HL104156 / HL / NHLBI NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States
R01 AG031287 / AG / NIA NIH HHS / United States

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