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Chunk #30 — DISCUSSION — Limitations and Strengths

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Generalization of variants identified by genome-wide association studies for electrocardiographic traits in African Americans.
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Another limitation to both the discovery and the generalization analyses was our liberal significance threshold. For discovery, a conservative Bonferroni threshold to correct for multiple testing is the generally accepted 5.0×10−8. Given our small sample size and this conservative threshold, we had sufficient power to detect large genetic effect sizes; however, these effects are not realistic given previously reported candidate gene and GWAS findings for these traits. To address this limitation, we arbitrarily choose a significance threshold of 1.0×10−6 to identify possible real associations that would be missed by the conservative significance threshold. For generalization, we declared a generalization as having a consistent direction of effect and meeting a liberal significance threshold of p<0.05. Given that the generalization analysis was limited to only a subset of loci that was previously identified, a genome-wide correction for multiple testing was not necessary.