observed, including rs1362178 (P = 0.0034) from GRM8 and rs17168817 (P = 0.033) from CHRM2. None of the most associated markers (P < 0.01; N = 10) identified in these earlier studies were captured by the Illumina HumanHap 1M microarray and thus they could not be evaluated in the GWAS. Of the 18 previously reported SNPs associated with theta ERO and/or diagnoses of alcohol dependence, only rs2299498 from GRM8 (Chen et al., 2009) exhibits nominal significance (P = 0.028) in this study. Although these findings for CHRM2 and GRM8 are modest, they are not unexpected. Associations between GRM8 and CHRM2 and theta EROs were discovered primarily through linkage analysis, a method designed to detect a different set of genetic effects than those of GWAS [Manolio et al., 2009; Psychiatric GWAS Consortium Coordinating Committee, 2009]. In particular, if the previously observed linkage signals came from the joint effects of multiple rare or uncommon variants in these genes, we would not expect to detect these genes in GWAS studies, which are designed to capture associations with common variants.
