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Chunk #25 — ONLINE METHODS — SNP selection for replication

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Meta-analysis and imputation refines the association of 15q25 with smoking quantity.
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In collaboration with two other groups carrying out similar meta-analysis of smoking related traits (ENGAGE15 and TAG16) we agreed to an in-silico replication strategy in which for each phenotype (SQ, EVER/NEVER, CURRENT/NON-CURRENT) each group would select 15 regions of the genome showing evidence for association, and summary data (p-values, β-estimate, β-estimate variances, sample sizes, GC-lambda estimates and sample sizes) would be shared across groups to facilitate replication. We selected the top 15 regions for each phenotype based on the p-values we obtained in our own meta-analysis. We excluded regions in which only a small number of cohorts contributed to the study because the information measure at the SNPs in the excluded cohorts were below our thresholds, or where the heterogeneity between the studies was high. Each selected region consisted of several SNPs showing evidence of association in our meta-analysis with p-values below 1e-5. For each of the three phenotypes the results from all the cohorts in all three concurrent studies were combined together using the same GC-corrected inverse-variance meta-analysis method described above. A full list of the selected regions and the summary information from all 3 phenotypes is given in Supplementary Table 2.