For the GWAS, linear regression was performed using PLINK to determine the association of each SNP to global cortical Aβ levels. An additive genetic model was specified and age, gender, and diagnosis (through a set of binary dummy variables indicating HC, EMCI, LMCI, or AD) were applied as covariates. To account for multiple comparisons, we employed a conservative threshold for genome-wide significant association (p < 5 × 10−8) based on a Bonferroni correction of one million independent tests.18 Haploview19 (http://www.broad.mit.edu/mpg/haploview/) was used to generate Manhattan and Q-Q plots and SNAP20 (http://www.broadinstitute.org/mpg/snap/) was used to obtain regional association plots for selected loci. Post-hoc analyses, including hierarchical linear regression, effect size calculations, and exploratory correlation and interaction studies using Bonferroni corrections for multiple comparisons, were performed using IBM SPSS Statistics for Windows, Version 20.0 (Armonk, NY).
