Genome-Wide Association Studies of the PR Interval in African Americans
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Key result
The genetic variant rs3922844 in the SCN5A gene was significantly associated with PR interval duration in African Americans, increasing the interval by 5.1 msec per minor allele.
Population
6,247 African American individuals from four cohorts (ARIC, CFS, JHS, MESA)
Design
Meta-analysis
Authors
Discussion
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Implication
May inform ancestry-specific conduction risk assessment; extends SCN5A-PR associations to African Americans with larger effect than in Europeans.
Study Design
Type
Observational (n=6,247)
Multicenter
Yes
Structured PICO
P
Population
6,247 African American adults from four population-based cohorts who underwent electrocardiographic assessment of PR interval duration.
E
Exposure
Genetic variants (single nucleotide polymorphisms) associated with PR interval duration
O
Outcome
PR interval durationsurrogate
Main Result
Mean Difference: 5.1 (95% CI 4.1–6.1)
p-value: p=3x10^-23
Common genetic variants in SCN5A, SCN10A, MEIS1, and TBX5 are significantly associated with PR interval duration in African Americans, with the SCN5A signal showing a stronger effect than in individuals of European ancestry.
Limitations
- Risk of false positive associations due to multiple testing in genome-wide association studies
- Underpowered to detect common variants of small effect and rare variants
- Measurement error in PR duration and heterogeneity between cohorts
- Potential population stratification or confounding by ancestry
- Large-scale resequencing and functional experiments are necessary to identify causal variants
Cite This Study
Smith et al. (2011) conducted an observational in PR interval duration (n=6,247). Genetic variant rs3922844 in SCN5A vs. Major allele was evaluated on PR interval duration (beta = 5.1 msec per minor allele, 95% CI 4.1-6.1, p=3x10^-23). The genetic variant rs3922844 in the SCN5A gene was significantly associated with PR interval duration in African Americans, increasing the interval by 5.1 msec per minor allele.
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