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Chunk #13 — MATERIALS AND METHODS — Neuroimaging analysis of GWS loci:

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Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.
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We examined whether GWS SNPs identified in our COGA GWAS of ANYDEP (i.e., rs34066662, rs75168521, rs1890881; the indel was not available) were associated with reward-related brain function in the Duke Neurogenetics Study (DNS), an independent neuroimaging sample containing non-Hispanic AA (n=118) and EA (n=481) undergraduate students aged 18–22 years31 (see Supplemental Text). A number guessing paradigm was used to elicit ventral striatum (VS) reactivity associated with positive and negative feedback linked to monetary gains and losses while bold-oxygen-level dependence (BOLD) functional magnetic resonance imaging (fMRI) data were acquired53. Statistical Parametric Mapping version 8 (SPM8) software was used to extract parameter estimates for the contrast of Positive Feedback > Negative Feedback from maximal voxels within left and right VS regions of interest (ROIs). Imaging acquisition protocol, task, ROIs, and preprocessing details are described in the Supplemental Text. Extracted parameter estimates from VS activity in each hemisphere were regressed on genotype (coded as 0 vs 1 or more copies of the minor allele) of GWS loci while co-varying for sex, and 3 (AA) or 2 (EA) ancestral principal components using Full Information