A telescope GWAS analysis strategy, based on SNPs-genes-pathways ensamble and on multivariate algorithms, to characterize late onset Alzheimer's disease
| Autor: | Squillario, Margherita, Abate, Giulia, Tomasi, Federico, Tozzo, Veronica, Barla, Annalisa, Uberti, Daniela, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Clifford, Jack R., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulam, M. Marcel, Potter, William, Snyder, Peter, Montine, Tom |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Aging Multivariate statistics Gene regulatory network lcsh:Medicine Genome-wide association study Neurodegenerative Alzheimer's Disease Machine Learning 0302 clinical medicine Genetics research 2.1 Biological and endogenous factors Gene Regulatory Networks Aetiology lcsh:Science Multidisciplinary Single Nucleotide Alzheimer's disease Magnetic Resonance Imaging Neurological Algorithm Algorithms Biotechnology Alzheimer's Disease Neuroimaging Initiative Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Article 03 medical and health sciences Alzheimer Disease Genetics Acquired Cognitive Impairment Humans Genetic Predisposition to Disease Allele Polymorphism Alleles Genetic association Gene Expression Profiling Human Genome lcsh:R Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Alzheimer’s Disease Neuroimaging Initiative Brain Disorders Gene expression profiling 030104 developmental biology Positron-Emission Tomography Dementia lcsh:Q 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Scientific reports, vol 10, iss 1 Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Medical Biophysics Publications Scientific Reports |
| Popis: | Genome–wide association studies (GWAS) have revealed a plethora of putative susceptibility genes for Alzheimer’s disease (AD), with the sole exception of APOE gene unequivocally validated in independent study. Considering that the etiology of complex diseases like AD could depend on functional multiple genes interaction network, here we proposed an alternative GWAS analysis strategy based on (i) multivariate methods and on a (ii) telescope approach, in order to guarantee the identification of correlated variables, and reveal their connections at three biological connected levels. Specifically as multivariate methods, we employed two machine learning algorithms and a genetic association test and we considered SNPs, Genes and Pathways features in the analysis of two public GWAS dataset (ADNI-1 and ADNI-2). For each dataset and for each feature we addressed two binary classifications tasks: cases vs. controls and the low vs. high risk of developing AD considering the allelic status of APOEe4. This complex strategy allowed the identification of SNPs, genes and pathways lists statistically robust and meaningful from the biological viewpoint. Among the results, we confirm the involvement of TOMM40 gene in AD and we propose GRM7 as a novel gene significantly associated with AD. |
| Databáze: | OpenAIRE |
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