Research On Alzheimer's Disease Genetic Variants Using Bioinformatics Methods

Alzheimer's disease(AD)is a common neurodegenerative disease caused by genetic and environmental factors.With the aging of the world and China,AD afflicts millions of families in China.Therefore,the research on the basis and application of AD is of great significance.With the development of high throughput gene chip and genome sequencing technology,the influence of genetic factors on AD has gradually deepened.However,72% of AD genetic factors are still unknown.At the same time,there is no clear and effective drug treatment for AD,and early prevention is particularly critical.Therefore,exploring the genetic factors and controllable environmental AD factors may provide theoretical basis for risk assessment and early diagnosis of AD.Based on the bioinformatics method,this paper analyzed the genome,transcriptome,imaging,pathology,social environment and physiological environment data.In the study of genetic factors,this paper focused on the genetic differences in different populations,gene expression,pathological features and biological pathways of significant enrichment of AD genetic variants.In the research of environmental factors,this paper deeply studied the social and physiological environmental factors related to AD.In view of the fact that 72% of the genetic factors of AD are unknown,this paper puts forward the viewpoint that the increase of sample size is helpful to discover the potential genetic factors of AD.To validate the above viewpoint,this paper identifies AD-related biological pathways based on large sample GWAS data and 599 dependent genetic variants with P<5.00E-08.The results of this study further validate the correlation between immune,lipid metabolic pathways and AD.At the same time,this paper identified five new biological pathways related to bacterial and viral infection and the correlation of AD were found,including Herpes simplex infection(hsa05168),Tuberculosis(tuberculosis,hsa05152),Epstein-Barr virus infection(Epstein-Barr virus,hsa05169),Staphylococcus aureus infection(hsa05150),Influenza A(influenza A virus,hsa05164).These findings broaden the understanding of the pathogenesis of AD and provide potential target information for further study of the pathogenesis of AD.Until now,GWAS have identified AD genetic variants located in the non-coding region of the gene.Hence,their functions are unknown.This paper puts forward the viewpoint that AD genetic variants in the non-coding region of the gene regulate the expression of target genes to perform its biological functions and affect the pathological characteristics of AD.In order to verify the above viewpoint,this paper selected 22 indenpent AD genetic variants from the 599 dependent genetic variants with P<5.00E-08.The epigenetic function analysis showed that these 22 indenpent AD genetic variants were active in peripheral blood.This paper identified that 11 AD genetic variants rs35349669,rs6733839,rs10948363,rs11771145,rs2718058,rs28834970,rs2373115,rs983392,rs10498633,rs6656401,and rs190982 could significantly regulate the target gene expression in peripheral blood.Five genetic variants including rs6656401,rs1476679,rs9331896,rs10838725 and rs7274581 could significantly regulate the expression of target genes in normal cognitive individuals.Two genetic variants including rs6656401 and rs2373115 could significantly regulate the expression of target genes in cognitive impaired individuals.Based on pathological data,only rs190982 variant has significant effect on cognitive function.These results indicate that AD genetic variation tends to regulate target gene expression in peripheral blood,which provides new clues for further understanding the molecular origin of disease.In view of the inconsistency of the association results of AD genetic variants in Chinese,European and American populations,this paper selected rs3851179,rs3865444,rs2373115,rs11767557 variants from the 22 indenpent AD genetic variants,and evaluated the susceptibility of these genetic variants to AD risk in Chinese population through a large number of literature searches and integrated large data analysis.Meanwhile,this paper compared the genetic differences between Chinese and European populations.The study found that rs3851179 variant was significantly associated with AD in Chinese population,and there was no genetic difference between Chinese population and European and American population.The variants of rs3865444,rs2373115 and rs11767557 were not significantly associated with AD in Chinese population,and there were genetic differences between Chinese population and European and American population.Based on the above findings,this paper clarifies that population genetic heterogeneity is the main reason causing the inconsistency of AD candidate gene studies in China,and provides theoretical support and genetic evidence for further study of AD specific genetic variation in Chinese.In view of the hypothesis that AD results from both genetic and environmental factors,this paper further identifies the social and physiological environmental factors that affect AD.Based on large-scale GWAS data and Mendelian randomization method,this paper evaluated the effects of social and physiological environmental factors(individual education level,blood calcium level and vitamin E level)on AD.This paper found that the risk of AD decreased by about 35% for every 4.2 years increase in the average population.This studye found that for every 0.5-mg/dL increase in blood calcium levels in the general population,the risk of AD decreased by about 44%.However,there is no significant causal relationship between the increase or decrease of vitamin E level and the risk of AD.These findings provide new clues and ideas for the identification of AD controllable risk factors.In summary,this paper evaluated the genetic and environmental factors related to AD based on bioinformatics methods.In terms of genetic factors,this paper found that:(1)AD genetic variants show significant enrichment in immune,lipid metabolism,bacterial and viral infection pathways;(2)AD genetic variants tend to regulate target gene expression in peripheral blood;(3)AD genetic variants have population genetic differences among Chinese,European and American populations.Meanwhile,this paper found that longer education years and higher serum calcium levels contribute to reduced risk of AD.These findings will provide a solid theoretical basis for further study of the pathogenesis and early prevention of AD.