Autor:innen:
Fabian Fußer, Frankfurt am Main (Germany)
Maja Adel, Frankfurt am Main (Germany)
Andreas Reif, Frankfurt am Main (Germany)
Silke Matura, Frankfurt am Main (Germany)
David Prvulovic, Frankfurt am Main (Germany)
Johannes Pantel, Frankfurt am Main (Germany)
Tarik Karakaya, Frankfurt am Main (Germany)
Alzheimer´s disease (AD) is a highly heritable, genetically heterogeneous neurodegenerative disease. Apart from Apolipoprotein E (ApoE) accounting for the highest genetic risk to develop AD, genome-wide association studies (GWAS) identified a number of gene variants increasing an individual’s risk for AD. These include single nucleotid polymorphisms (SNPs) of genes like CLU, PICALM, CR1, ABCA7, or CD33 (Harold et al., 2009; Hollingworth et al., 2009). By combining these individual effects of multiple genetic factors, polygenic risk scores (PRS) express the cumulative genetic risk to develop AD (Logue et al., 2019; Fan et al, 2019). In our study we associate PRS with cognitive function in healthy older subjects to evaluate whether subtle cognitive deficits can be attributed to genetic risk for AD.
90 cognitively healthy elders (mean age: 66 years, 55-78 years) were assessed with the CERAD neuropsychological test battery and the California Verbal Learning Test (CVLT). PRS are calculated following recent recommendations (Chasioti et al., 2019) including quality control (PLINK), and accounting for linkage disequilibrium (LD). We compare different approaches such as LDpred (Vilhjálmsson et al., 2015) and Lassosum (Mak et al., 2017) considering ApoE genotype as a covariate (Stocker et al., 2018).
We expect that distinct cognitive alterations are associated with PRS, and that cognitive trajectories might be predicted by PRS even in stages preceding the clinical onset of AD (Mormino et al., 2016).