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Chunk #9 — Materials and Methods — Discovery study samples, the FTND and quality control

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Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.
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COGEND, a community-based case–control study of nicotine-dependent smokers vs smokers who never developed nicotine-dependence symptoms, began recruiting participants in 2001 from St. Louis and Detroit through telephone screening to identify current smokers aged 25 to 44 years old.3 The FTND was administered to determine study eligibility. Current smokers with an FTND score of ⩾4 were recruited as nicotine-dependent cases, and smokers who reported >100 cigarettes during their lifetime but an FTND score of 0 or 1 were recruited as controls. COGEND participants were genotyped on either the Illumina Human1M-Duo BeadChip array, as part of SAGE,9 or the Illumina HumanOmni2.5 BeadChip array as part of GENEVA.20 In each subset, genotyped SNPs with a call rate >98% and HWE P⩾1 × 10−4 were retained. We combined the subsets and removed duplicated participants and first-degree relatives. To circumvent bias that may arise from conducting imputation on subjects genotyped on different arrays, we carried forward only the SNPs genotyped at the intersection of the different arrays.21 After applying our standard QC procedures (Supplementary Information) on the combined COGEND sample, there remained 1935 participants for our study.