For each candidate gene we tested the null hypothesis that no SNP within 20 kb upstream of the start of transcription and 10 kb downstream of the stop of transcription (based on NCBI build 35.1) was associated with smoking behaviors using a parametric permutation procedure that allows for covariate adjustment. We compared the smallest observed p-value for any SNP in the candidate gene region to the empirical null distribution of the smallest p-value based on 20,000 random permutations. This approach provides a gene-level p-value that is adjusted for both the number of SNPs in the gene region and their linkage disequilibrium structure.
