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Chunk #47 — ONLINE METHODS — Estimation of the number of associated loci

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Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
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To estimate the total number of newly associated loci selected for the iCOGS array, we first used the set of 29,807 SNPs selected from the GWAS and not selected for fine mapping, to exclude previously known loci. We then defined a set of 10,668 SNPs that were uncorrelated (r2 < 0.1 between any pair) and determined the number of loci for which the estimated effect size in the iCOGS stage was in the same direction as in the combined GWAS and the number of loci for which the effect was in the opposite direction. Similar results were obtained using cutoffs of r2 < 0.05 and r2 < 0.2. On the assumption that none of the loci with effects in opposite directions in the two stages were associated with disease, the number of loci associated with disease can be estimated as the difference between the number of loci with effects in the same direction and the number with effects in opposite directions. This, however, is an underestimate because loci with weak effects may have estimated effects in opposite directions in the