Our primary single SNP association analyses of case-control status use logistic regression models to correct for significant covariates of gender and sample source site (US or Australia) (Table 1). The non-genetic base model is: ln(P1−P)=α+β1g+β2s, where P is the probability of being a case, g is gender (0=male, 1=female) and s is site (0 for US, 1 for Australia). Genotype status at each marker, coded as an ordinal variable, is then added to the model and tested for significance by the standard likelihood chi-square statistic with one degree of freedom (df). The ordinal coding corresponds to a log-additive (multiplicative) model for the number of copies of the risk allele, defined as the allele more common in cases than controls. This primary test differs from the test used in (Bierut et al., 2007; Saccone et al., 2007a), which included a genotype by gender interaction term to allow detection of loci having differential effect in males versus females. In our focused nAChR study here, we first tested for SNP effect only; then, for SNPs significant in that primary test, we investigated possible gender effects and alternative modes of inheritance.
