Genotypes within pedigrees are correlated, The generalized estimating equations (GEE) method (Liang and Zeger 1986; Zeger and Liang 1986), an extension of the quasi-likelihood approach (Wedderburn 1974), is used to analyze correlated data, longitudinal data and family data (Chen et al 2004; Hanley et al 2003; Lange et al 2003). In the present study, GEE as implemented in SPSS v15 (SPSS Inc.), was implemented to model CD using a two-way interaction between the risk SNP and other SNPs of CNR1. The model applied a logit link function and Pearson chi-square estimating method, while adjusting for sex and age. The working correlation matrix was set as unstructured, and maximum iteration was set as 100,000. For GEE there is no prior assumption for data distribution, and since the number of unaffecteds in our family sample was limited, for GEE analysis, we increased the control sample size by pooling 403 EA controls and 48 AA controls from our case-control samples with the corresponding family samples.
