A telescope GWAS analysis strategy, based on SNPs-genes-pathways ensamble and on multivariate algorithms, to characterize late onset Alzheimer's disease.

Scientific Reports
Margherita SquillarioAlzheimer’s Disease Neuroimaging Initiative

Abstract

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 ...Continue Reading

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Citations

Feb 20, 2021·Mechanisms of Ageing and Development·Marianne NygaardJonas Mengel-From
Jul 6, 2021·Frontiers in Neuroscience·Ann M SaundersWilliam Kirby Gottschalk

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Methods Mentioned

BETA
genotyping

Software Mentioned

Group
PALLADIO
SKATO
SKAT

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