A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans
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A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans. / Ilkhanoff, Leonard; Arking, Dan E; Lemaitre, Rozenn N; Alonso, Alvaro; Chen, Lin Y; Durda, Peter; Hesselson, Stephanie E; Kerr, Kathleen F; Magnani, Jared W; Marcus, Gregory M; Schnabel, Renate B; Smith, J Gustav; Soliman, Elsayed Z; Reiner, Alexander P; Sotoodehnia, Nona; Candidate-Gene Association Resource (CARE) Consortium and the Cardiac Arrest Blood Study (CABS) Investigators.
In: J CARDIOVASC ELECTR, Vol. 25, No. 11, 11.2014, p. 1150-1157.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans
AU - Ilkhanoff, Leonard
AU - Arking, Dan E
AU - Lemaitre, Rozenn N
AU - Alonso, Alvaro
AU - Chen, Lin Y
AU - Durda, Peter
AU - Hesselson, Stephanie E
AU - Kerr, Kathleen F
AU - Magnani, Jared W
AU - Marcus, Gregory M
AU - Schnabel, Renate B
AU - Smith, J Gustav
AU - Soliman, Elsayed Z
AU - Reiner, Alexander P
AU - Sotoodehnia, Nona
AU - Candidate-Gene Association Resource (CARE) Consortium and the Cardiac Arrest Blood Study (CABS) Investigators
N1 - © 2014 Wiley Periodicals, Inc.
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Adult
KW - African Americans/genetics
KW - Aged
KW - Aged, 80 and over
KW - Atrial Fibrillation/diagnosis
KW - Case-Control Studies
KW - Cohort Studies
KW - Death, Sudden, Cardiac
KW - Female
KW - Genetic Variation/genetics
KW - Humans
KW - Male
KW - Middle Aged
KW - NAV1.5 Voltage-Gated Sodium Channel/genetics
KW - Prospective Studies
KW - Risk Factors
KW - Single-Blind Method
U2 - 10.1111/jce.12483
DO - 10.1111/jce.12483
M3 - SCORING: Journal article
C2 - 25065297
VL - 25
SP - 1150
EP - 1157
JO - J CARDIOVASC ELECTR
JF - J CARDIOVASC ELECTR
SN - 1045-3873
IS - 11
ER -
