Abstract
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.
Highlights
Alzheimer’s disease (AD) is a complex and severe neurodegenerative disorder
Our results indicated that both GM and WM volume adjusted for age, gender and intracranial volume in AD patients are smaller than that in normal control subjects (p-value < 2.2 × 10−16 and p-value = 0.0002815, respectively)
Current studies have demonstrated that many genetic variations are associated with AD
Summary
Alzheimer’s disease (AD) is a complex and severe neurodegenerative disorder It is characterized by progressive deterioration in cognition and behavior, which seriously affects people’s daily life (Hu et al, 2017; Jiang et al, 2017; Liu et al, 2018). The polygenic risk score (PRS) was described to depict quantitatively the combined effect of SNPs on disease risk (International Schizophrenia Consortium, 2009). Brain-associated endo-phenotypes were commonly used to analyze the effect of disease-associated SNPs. Late-onset AD PRS was used to predict hippocampus function (Xiao et al, 2017). Terwisscha van Scheltinga et al (2013) found schizophrenia-associated genetic risk variants jointly modulate total brain and white matter volume by PRS approach
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
