There is substantial phenotypic overlap between the CC and FS models used to capture the comorbidity and shared genetic risk among the ADs, and as expected, there was a high degree of concordance in the association signals genome-wide (Supplementary Table S3). The most significantly associated SNPs (p<.0.05) have very high correlation of association effects, suggesting they are tapping into strongly related AD risk factors. We note that, overall, the FS phenotype identified a larger number of associated SNPs than the CC model. This is likely due to several reasons: (1) this approach combines disorder information to capture individual differences on an underlying latent AD liability; (2) for high prevalence disorders, quantitative variables generally have greater power for genetic association than categorical variables (34;35); (3) the FS models generally involve larger sample sizes since they also include the subjects with subthreshold ADs (score=1); and (4) the FS model produces a phenotype that incorporates the observed relationship information (covariance) between the individual ADs. These findings support the use of quantitative phenotypic factors scores in future GWAS of comorbid psychiatric disorders assessed in the same individuals.
