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Chunk #5 — METHODS — Genome-wide association study of DSM-defined nicotine dependence (DSM-NicDep)

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Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.
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We performed meta-analyses of GWASs of DSM-defined nicotine dependence (hereafter referred to as “DSM-NicDep”) across a total of 18 cohorts, three of which included samples of multiple ancestries, using a sample size-weighted meta-analysis implemented in METAL16. We used nicotine-exposed controls where possible (see Supplemental Materials for more details on each cohort). Genetic ancestry similarity was inferred by comparing an individual’s genome to the genomes from global reference populations using statistical methods such as principal components analysis, although exact methods varied somewhat across cohorts. There were 16 cohorts with samples that were most genetically similar to European ancestry global reference populations, 4 with samples that were most genetically similar to African ancestry global reference populations, and one cohort whose participants were most genetically similar to East Asian ancestry global reference populations (hereafter referred to as European, African, or East Asian ancestries). All GWAS controlled for age, sex, and 10 principal components; more details, including cohort-specific covariates, are provided in Supplemental Table 1. Twelve cohorts provided summary statistics, while five cohorts provided individual genotype and phenotype data for analysis (Supplemental Table 1).