Squillario, M;
Abate, G;
Tomasi, F;
Tozzo, V;
Barla, A;
Uberti, D;
Alzheimer’s Disease Neuroimaging Initiative;
(2020)
A telescope GWAS analysis strategy, based on SNPs-genes-pathways ensamble and on multivariate algorithms, to characterize late onset Alzheimer's disease.
Scientific Reports
, 10
(1)
, Article 12063. 10.1038/s41598-020-67699-8.
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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 novel gene significantly associated with AD.
| Type: | Article |
|---|---|
| Title: | A telescope GWAS analysis strategy, based on SNPs-genes-pathways ensamble and on multivariate algorithms, to characterize late onset Alzheimer's disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-020-67699-8 |
| Publisher version: | http://dx.doi.org/10.1038/s41598-020-67699-8 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Alzheimer's disease, Genetics research, Machine learning |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10107670 |
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