To identify genetic variants contributing to genetic susceptibility shared across the ADs, we applied and compared two complementary phenotypic approaches: (1) categorical CC comparisons, and (2) quantitative phenotypic FS. For CC comparisons, AD cases were assigned to subjects meeting criteria for any lifetime AD (ANX=2) while control subjects were “super-normal”, i.e., having few or no clinical anxiety symptoms (ANX=0); those with subsyndromal ADs (ANX=1) were excluded from the CC analyses. For FS analyses, first exploratory factor analyses were conducted using Mplus (version 4) (39) separately in each sample, finding evidence for a single common factor model by scree plots. This was followed by confirmatory factor analyses that estimated a single FS for each subject from this common AD liability factor. (See Supplement for details of phenotype construction.) Association analyses were then performed in each study independently with imputed SNP dosages under an additive genetic model using logistic regression for CC phenotype and linear regression for quantitative FS phenotype. As covariates, we used sex and age at interview, as they were significant predictors of the phenotypes. Ancestry principal components were estimated
