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Chunk #11 — Methods — DNA preparation and assessment of allelic frequencies

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Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples.
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Each array was analyzed as described [9,11,33,34], with background values subtracted, normalization to the highest values noted on the array, averaging of the hybridization intensities from the array cells that corresponded to the perfect match "A" and "B" cells, calculation of "A/B ratios" by dividing average normalized A values by average normalized B values, arctangent transformations to aid combination of data from arrays hybridized and scanned on different days, and determination of the average arctangent value for each SNP from the 4 replicate arrays. A "t" statistic for the differences between abusers and controls was generated as described [9,11,33,34] for each SNP. We focused on SNPs that displayed t statistics with p < 0.05 for abuser/control differences. We sought evidence for clustering of these SNPs by focusing on chromosomal regions in which at least three of these outlier SNPs, assessed by at least two array types, lay within 25 Kb of each other. We term these clustered, nominally-positive SNPs "clustered positive SNPs", and focus our analyses on regions in which they lie.