The present study has a number of strengths. First, it is based on large, well-characterized samples of AD cases and screened controls. Second, the gene studied encodes a protein that may have important implications for understanding both the etiology and pharmacological treatment of AD. Third, we examined multiple SNPs in GRIK1, which were chosen based on potential functional effects related either to a glutamine-to-arginine amino acid coding change that affects glutamate receptor function (Seeburg et al. 1998; Seeburg & Hartner 2003) or to potential alternative splice sites resulting in isoforms that could influence receptor assembly and intracellular trafficking of receptors that contain the GluR5 subunit. Although the study is limited by the fact that the control sample was drawn from Connecticut, while the majority of cases were recruited from sites around the United States, analysis of ancestry informative markers revealed no difference in ancestry proportion as a function of diagnostic group. Similarly, although the age and sex distributions differed by diagnostic group, these differences were not correlated with genotype for the seven SNPs examined. Thus, these potential confounders did not
