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Chunk #13 — Results — Independent secondary signals at known loci

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Discovery of novel heart rate-associated loci using the Exome Chip.
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The secondary SNVs at CCDC141, ACHE and KIAA1755 are non-synonymous variants. Furthermore, the SNVs at CCDC141 and KIAA1755 are low-frequency with minor allele frequencies (MAFs) of 3.6 and 1.7%, respectively. Secondary signals have also recently been observed at four of the five loci (CD46, CCDC141, SLC35F1 and ACHE) in UK Biobank data (17), since completion of our meta-analysis. At CD46, our secondary SNV (rs2745967) is in high LD (r2 = 0.78) with the secondary SNV (rs2745959) reported in UK Biobank, so likely to be the same signal. At CCDC141 our secondary variant is exactly the same SNV as from UK Biobank (rs10497529). Similarly, at SLC35F1, our secondary SNV (rs12210810) is in very high LD (r2 = 0.98), so is likely to be the same signal. Hence at these three known loci (CD46, CCDC141, SLC35F1), all existing data suggest there are two independent signals of association. At the ACHE locus, our secondary SNV (rs542137; ∼38 kb and r2 < 0.2 from the published SNV) is not in LD (r2 < 0.2) with the secondary SNV from UK Biobank (rs140367586; ∼659 kb