SNP genotypes were evaluated for standard summary measures including genotyping rates, allele and genotype frequencies, and Hardy-Weinberg equilibrium tests. Standard case/control allelic χ 2 analyses were used to test the association of SNPs with dichotomized FTND, as well as the Cochran-Armitage trend test using the computer program, PLINK [69]. Empirical significance levels of allelic tests were evaluated by phenotype-genotype permutation testing using the PLINK adaptive mode. The logistic regression analyses reported in Tables 3–4 and Figure 2 were computed using SYSTAT 10.2 (Richmond, CA: SYSTAT Software Inc.). Dummy coding was used for haplotype and sex, while ordinal coding was used for age of onset of daily smoking. Haplotype estimation and individual assignment were carried out on genotypic data using fastPHASE [70], and independently evaluated using the EM algorithm implemented in SNPHAP (http://www-gene.cimr.cam.ac.uk/clayton/software). Haplotype-based association analyses for omnibus and haplotype-specific tests were carried out using PLINK. To evaluate potential population stratification effects, the UT and WI cohorts were analyzed for population admixture using STRUCTURE [71] on 94 non-related loci and an assumed population of 2. No significant admixture was observed, supporting
