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Chunk #5 — RESULTS — Follow-up of suggestive loci in additional samples

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Genome-wide association study identifies 30 loci associated with bipolar disorder.
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Of the 19 variants that were genome-wide significant in the discovery GWAS, 8 were not genome-wide significant in the combined analysis (Table 1B), and 11 were non-significant in one-tailed association tests in the follow-up samples (p>0.05 in Table 1). Still, the follow-up results for these 19 variants are clearly non-null in aggregate: all 19 had consistent directions of effect between discovery GWAS and follow-up (9.5 expected by chance, binomial test p=4×10−6), and eight of the 19 had follow-up 1-tailed p<0.05 (1 expected by chance, sign test p=2×10−6). Using effect sizes corrected for winner’s curse 27,28 for each of the 19 variants that were genome-wide significant in the GWAS, we calculated power to achieve significant results (1-tailed p<0.05) in the follow-up samples or genome-wide significance in combined analysis (Supplementary Note, Supplementary Table 6, Supplementary Figure 4). We found that the number of variants significant in follow-up is close to expectation (8 observed with follow-up p<0.05, 8.26 expected, Poisson binomial p = 0.57), and that 11 variants achieving genome-wide significance in the combined analysis is also within the expected range (p =