Sex-specific genetic predictors of Alzheimer ’s disease biomarkers

AbstractCerebrospinal 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. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 withinSERPINB1 (p = 0.04) and rs13115400 nearLINC00290 (p = 0.002). These loci showed stronger associations among females (β = − 0.03,p = 4.25 × 10−8;β = 0.03,p = 3.97 × 10−8) than males (β = − 0.02,p = 0.009;β = 0.01,p = 0.20). Higher levels of expression ofSERPINB1, SERPINB6, andSERPINB9 in PFC was associated with higher levels of amyloidosis among females (correctedp values  <  0.02) but not males (p > â...
Source: Acta Neuropathologica - Category: Neurology Source Type: research