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Chunk #17 — Methods — Statistical Analyses

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The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach.
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Following the individual SNP association tests within the testing sample, ”risk scores” for each SNP were then calculated for each individual in the testing sample by multiplying the number of minor alleles at that SNP by its training-sample-estimated regression coefficient. For the purpose of estimating risk scores, if an individual was missing a genotype for a scoring SNP, they were allocated the mean number of minor alleles (although the missingness rates among the selected SNPs were low, with a median rate of 0.1% and all SNPs having missingness rates less than 2%). To identify the best aggregate SNP score in the testing sample, SNPs were incorporated one at a time to the calculation of a total risk score, in order of ascending p-value resulting from the initial association tests run in the training sample, until the variance in the testing sample explained by the included SNPs began decreasing. That is, individual SNP scores were summed across all SNPs to be included in the score, i.e. score = ∑1-i (N Minor Alleles for SNP i*B SNP i), where B is the regression weight for the SNP predicting the standardized residuals of cocaine dependence symptom counts in the training sample.