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Chunk #55 — Materials and Methods — Non-European ancestry analyses

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Discovery of novel heart rate-associated loci using the Exome Chip.
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Association results were also received for non-European samples. Analysis and QC were performed as described for the European data. A meta-analysis was performed centrally in seqMeta for AA ancestry, combining data from the five AA cohorts. Study-level results remained for HIS and CH ancestries (from only the MESA cohort), in order to consider the three non-European ancestries (AA, CH and HIS) separately from stratified analyses. Due to the smaller sample sizes, power calculations were performed using the Genetic Power Calculator (35), based on the average percent trait variance explained per locus being 0.04%, according to the recently published results from 64 validated HR loci explaining ∼2.5% of HR variance (17). To assess the level of heterogeneity by ancestry in non-European data, we performed a look-up of SNVs at the 12 published HR loci covered on the Exome Chip, extracting results for these variants from each of the AA, CH and HIS results. We restricted our primary discovery analysis to Europeans only after finding a lack of significant validation and concordance between EUR and non-EUR data for previously reported HR variants.