Prioritization of Genetic Variants Predisposing to Alzheimer's Disease in Young Healthy Bulgarian Individuals Using Centenarian Exomes

Abstract

The present study aims to identify pathogenic/risky variants in the exomes of healthy young individuals predisposing to Alzheimer's disease (AD) by their validation in centenarian's exomes. The group of Bulgarian centenarians included 32 individuals (mean age 102.4) without AD diagnosis and the matched control group of 61 young healthy individuals (mean age 21.9). Two DNA pools were constructed with equimolar amounts of DNA from each participant and whole exome sequencing analysis (WES) was performed. We examined the WES data for pathogenic or risky SNPs predisposing to AD. Of altogether 1929 variants selected from DisGeNet database for association with AD, only 174 (9.02%) were detected in our WES data. One hundred and fifty-two (152) SNPs were present in both studied groups, 8 in centenarians and 14 in controls only. Seven variants have significantly higher frequency in young individuals or absence in centenarians. Based on sufficiently unambiguous literature data, we nominated rs63750264 in APP, rs429358 in APOE, rs1800562 in HFE variants for predisposition to AD in young individuals. To a lesser extent, the carriership of rs2070045 in SORL1, rs6265 in BDNF, rs769449 in APOE, rs4988514 in SST can increase the risk to AD development. These variants could find implication in the Alzheimer's disease estimation in young individuals before the onset of clinical symptoms.