Autopsy measures of Alzheimer’s disease neuropathology have been leveraged as endophenotypes in previous genome-wide association studies (GWAS). However, despite evidence of sex differences in Alzheimer’s disease risk, sex-stratified models have not been incorporated into previous GWAS analyses.

We looked for sex-specific genetic associations with Alzheimer’s disease endophenotypes from six brain bank data repositories. These cohorts (LOAD, Mayo, ACT, NACC, ROS/MAP, TGEN) contained neuropathology and genotype data for 2,701 males and 3,275 females. Neuropathology data were harmonized across cohorts and genotypes underwent standard quality control and imputation (genome build 37). Stratified GWAS assessed for associations with neuropathology within males and females separately and genome-wide significant loci in each sex were tested for sex interactions.