A Multi-Marker Genetic Association Test Based on the Rasch Model Applied to Alzheimer’s Disease

Wenjia Wang, Jonas Mandel, Jan Bouaziz, Daniel Commenges, Serguei Nabirotchkine, Ilya Chumakov, Daniel Cohen, Mickaël Guedj and the Alzheimer’s Disease Neuroimaging Initiative

PLOS ONE, 2015, vol. 10, issue 9, 1-19

Abstract: Results from Genome-Wide Association Studies (GWAS) have shown that the genetic basis of complex traits often include many genetic variants with small to moderate effects whose identification remains a challenging problem. In this context multi-marker analysis at the gene and pathway level can complement traditional point-wise approaches that treat the genetic markers individually. In this paper we propose a novel statistical approach for multi-marker analysis based on the Rasch model. The method summarizes the categorical genotypes of SNPs by a generalized logistic function into a genetic score that can be used for association analysis. Through different sets of simulations, the false-positive rate and power of the proposed approach are compared to a set of existing methods, and shows good performances. The application of the Rasch model on Alzheimer’s Disease (AD) ADNI GWAS dataset also allows a coherent interpretation of the results. Our analysis supports the idea that APOE is a major susceptibility gene for AD. In the top genes selected by proposed method, several could be functionally linked to AD. In particular, a pathway analysis of these genes also highlights the metabolism of cholesterol, that is known to play a key role in AD pathogenesis. Interestingly, many of these top genes can be integrated in a hypothetic signalling network.

Date: 2015
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138223 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 38223&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0138223

DOI: 10.1371/journal.pone.0138223

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone (plosone@plos.org).