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Chunk #22 — Results

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Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.
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GWAS analyses behaved well, with genomic control values for the GWAS across exome chip and UK Biobank imputed variants between 1.05 and 1.3. The intercept for LD Score regression ranged between .99 and 1.1, indicating absent or minimal effects of population stratification. (Per-study genomic controls can be found in Table S2.) A total of 171 loci were identified under the genome-wide significance threshold (p<5×10 −8), including 3, 11, 17, 93 and 47 loci for AgeSmk, CigDay, PckYr, SmkInit, and DrnkWk. A list of all sentinel variants within each locus is shown in Table S5. QQ plots and Manhattan plots are available in Figures S1 and S2. (Additional exploratory GWAS meta-analysis of individuals with significant African ancestry are provided in the Supplementary Note [including up to 8,974 individuals from three studies]; see also Table S3, Figure S3 and S4.) The genome-wide significant association results included known loci associated with smoking and alcohol use phenotypes. These included associations between smoking phenotypes and variants within the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor cluster, nicotine metabolism gene CYP2A6, and a locus near dopamine receptor DRD2. We also