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A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans.

TitleA common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans.
Publication TypeJournal Article
Year of Publication2014
AuthorsIlkhanoff L, Arking DE, Lemaitre RN, Alonso A, Chen LYee, Durda P, Hesselson SE, Kerr KF, Magnani JW, Marcus GM, Schnabel RB, J Smith G, Soliman EZ, Reiner AP
Secondary AuthorsSotoodehnia N
Corporate AuthorsCandidate-Gene Association Resource(CARE) Consortium and the Cardiac Arrest Blood Study(CABS) Investigators
JournalJ Cardiovasc Electrophysiol
Volume25
Issue11
Pagination1150-7
Date Published2014 Nov
ISSN1540-8167
KeywordsAdult, African Americans, Aged, Aged, 80 and over, Atrial Fibrillation, Case-Control Studies, Cohort Studies, Death, Sudden, Cardiac, Female, Genetic Variation, Humans, Male, Middle Aged, NAV1.5 Voltage-Gated Sodium Channel, Prospective Studies, Risk Factors, Single-Blind Method
Abstract

OBJECTIVE: We examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans.

BACKGROUND: The SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger population-based studies are needed to validate these findings. The association of this variant with AF has not been fully explored.

METHODS: Using genotyping data on over 7,000 African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC], Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD using a population-based case-control study of SCD Cardiac Arrest Blood Study (CABS).

RESULTS: Meta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration (β = -4.1 milliseconds; P = 2.2×10(-6) ), but not significantly associated with QRS or QT intervals. In meta-analyses of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 × 10(-4) ). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly, S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases; P = 0.29).

CONCLUSION: The common SCN5A variant, rs7629265, is associated with increased AF risk and shorter PR interval among African Americans. In contrast to prior reports, we found no evidence of association of rs7629265 or rs7626962 (S1103Y) with SCD risk in the general population.

DOI10.1111/jce.12483
Alternate JournalJ Cardiovasc Electrophysiol
PubMed ID25065297
PubMed Central IDPMC4454499
Grant ListM01-RR00425 / RR / NCRR NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
1RC1HL101056 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
M01RR00080 / RR / NCRR NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
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RC1 HL101056 / HL / NHLBI NIH HHS / United States
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N01HC95162 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
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R01 HL088456 / HL / NHLBI NIH HHS / United States
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HL 46380 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
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HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01 HL102214 / HL / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
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N01HC95165 / HL / NHLBI NIH HHS / United States
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HHSN268201100007C / / PHS HHS / United States
N01-HC-95171 / HC / NHLBI NIH HHS / United States
M01 RR000425 / RR / NCRR NIH HHS / United States
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HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
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HHSN268201100005C / HL / NHLBI NIH HHS / United States
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N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL071205 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
N01-HC-95161 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
1R01HL102214 / HL / NHLBI NIH HHS / United States
L30 HL074790 / HL / NHLBI NIH HHS / United States
N01-HC25195 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
1R01HL092577 / HL / NHLBI NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
M01 RR000080 / RR / NCRR NIH HHS / United States
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