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Chunk #10 — Materials and methods — Data analysis

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Genome-wide association study identifies genes that may contribute to risk for developing heroin addiction.
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To test for differences in allele frequency between the cases and controls for each of the variants within each ethnic group, a two sample non-parametric t-test was conducted. Multivariate permutation (Simon et al., 2004) was used to correct for multiple testing, and experiment-wise P values are reported. To perform permutation testing for the experiment-wise P value, the class labels were permuted and the t statistic values for each of the markers were recalculated. The maximum t statistic (corresponding to minimum P value) of all ~110,000 tests (one test for each marker) from this permutation was taken. This procedure was repeated for 3,003 permutations of the data in the Caucasian group. The value 3,003 was obtained by selecting 6 controls (or 8 cases) out of 14 pooled samples. The originally observed t statistic was compared to the distribution of t statistics composed of 3003 maximum t statistics to obtain the experiment-wise P value. For example, an experiment-wise P value of 0.035 means that 105 out of 3,003 permuted maximum t statistics were higher than or equal to our observed t statistic. The P value obtained by this method is called the multivariate P value.