Identification And Analysis Of Ch4 Brain Region Associated Genetic Variations In Alzheimer’s Disease

Alzheimer’s disease（AD）is a common neurodegenerative disease that severely affects the daily life of patient.The genome wide association study（GWAS）has revealed many genetic variants associated with AD,but the effect of each variant is weak.The polygenic risk score is used to quantitatively characterize the combined effects of genetic variants.On the other hand,the brain structure or function of AD patients has changed,and severe loss of cholinergic neurons in the Ch4 brain region in basal forebrain has occurred.In this article,polygenic risk score method was used to identify genetic variants associated with Ch4 brain region.I found that the volume of Ch4 brain region was significantly different between AD patients and normal samples(P<2.2×10^-16),and there was no difference in brain intracranial volume between the two groups（P=0.8633）.The polygenic risk score based on 29631 genetic variants was significantly associated with the risk of the disease risk(P=1.6×10^-11),which could explain 25.81%AD risk,and the higher polygenic risk score was related to the greater AD risk;The polygenic risk score based on 9536 genetic variants was significantly associated with the Ch4 volume(P=5.1×10^-13),which could explain 17.11%variance of Ch4 volume,and the higher polygenic risk score was related to the smaller Ch4volume;In addition,the effect of polygenic risk score on Ch4 volume was not similar between AD patients and normal control subjects.Using the intracerebral volume as a negative control,there was no significant relationship between the AD polygenic risk score and the intracerebral volume.By correlation analysis of 9536 genetic variants and Ch4 volume,468 genetic variants were individually associated with Ch4 volume（P<0.05）.Finally,GO and KEGG pathway enrichment analysis on these 468 genetic variants were performed using web-based tool WebGestalt.The first 10 pathways of the biological process in GO were mainly related to the growth and development of neuron and cell;The first 10 pathways of molecular function were mainly related to protein activity;The first 10 pathways of cellular components were mainly related to the structure of neurons,including cell body,dendrite and axon;Two pathways in the first 10 KEGG pathways were closely related to the occurrence of AD,including Alzheimer’s disease and ErbB signaling pathway.