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Chunk #12 — Materials and methods — GWAS enrichment analysis

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Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism.
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The summary statistics from a GWAS of alcohol dependence (PGC-AD) were provided by the Psychiatric Genetics Consortium Substance Use Dependence working group22 (Walters et al.). Summary statistics for the UKBB alcohol consumption (UKBB-AC) GWAS23 were provided by Dr. Toni Clarke. We also downloaded the summary statistics for Tobacco and Genetics (TAG) Consortium’s GWAS24 of cigarettes per day from the PGC website (https://www.med.unc.edu/pgc/results-and-downloads). SNPs from the PGC-AD and UKBB-AC studies were mapped to PFC expression quantitative trait loci (eQTLs) in 461 post-mortem brains from the Religious Orders Study and Memory and Aging Project (ROS/MAP)25 (Bennett et al). Enrichment analysis was performed for SNPs meeting the criteria of eQTL P < 5 × 10−8 in the ROSMAP dataset and tested for overrepresentation in GWAS of AD (PGC-AD), alcohol consumption (UKBB-AC) and TAG-CPD. Since there are a few loci that passed the genome-wide significance threshold in alcohol and smoking GWAS analysis, we tested the polygenicity of alcoholism and smoking by exploring the overenrichment in variants that passed nominal threshold of significance in these datasets. The enrichment analysis was focused on eQTLs for the