Polygenic Risk Score for Alzheimer's Disease Is Associated With Ch4 Volume in Normal Subjects

Alzheimer's disease (AD) is a common neurodegenerative disease. APOE is the strong genetic risk factor of AD. The existing genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) with minor effects on AD risk and the polygenic risk score (PRS) is presented to combine the effect of these SNPs. On the other hand, the volumes of various brain regions in AD patients have significant changes compared to that in normal individuals. Ch4 brain region containing at least 90% cholinergic neurons is the most extensive and conspicuous in the basal forebrain. Here, we investigated the relationship between the combined effect of AD-associated SNPs and Ch4 volume using the PRS approach. Our results showed that Ch4 volume in AD patients is significantly different from that in normal control subjects (p-value < 2.2 × 10^-16). AD PRS, is not associated with the Ch4 volume in AD patients, excluding the APOE region (p-value = 0.264) and including the APOE region (p-value = 0.213). However, AD best-fit PRS, excluding the APOE region, is associated with Ch4 volume in normal control subjects (p-value = 0.015). AD PRS based on 8070 SNPs could explain 3.35% variance of Ch4 volume. In addition, the p-value of AD PRS model in normal control subjects, including the APOE region, is 0.006. AD PRS based on 8079 SNPs could explain 4.23% variance of Ch4 volume. In conclusion, PRS based on AD-associated SNPs is significantly related to Ch4 volume in normal subjects but not in patients.