Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer’s disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes.

We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. This study leveraged data from seven studies of cognitive aging (Knight ADRC, ADNI1, ADNI2, BIOCARD, Mayo, Sweden, UPENN, UW) with 1,527 males and 1,509 females. CSF Ab42 and t-tau biomarker data were harmonized across cohorts and genotypes underwent standard quality control and imputation (genome build 37). A SNP*sex interaction GWAS evaluated differences in variant associations with pathology by sex and stratified GWAS assessed for associations with neuropathology within males and females separately.