edoc

A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility.

Bush, W. S. and McCauley, J. L. and DeJager, P. L. and Dudek, S. M. and Hafler, D. A. and Gibson, R. A. and Matthews, P. M. and Kappos, L. and Naegelin, Y. and Polman, C. H. and Hauser, S. L. and Oksenberg, J. and Haines, J. L. and Ritchie, M. D. and International Multiple Sclerosis Genetics Consortium, . (2011) A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility. Genes and immunity, Vol. 12, H. 5. pp. 335-340.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6005897

Downloads: Statistics Overview

Abstract

Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also increases power to detect weak main effects. We conducted a knowledge-driven interaction analysis of a GWAS of 931 multiple sclerosis (MS) trios to discover gene-gene interactions within established biological contexts. We identify heterogeneous signals, including a gene-gene interaction between CHRM3 (muscarinic cholinergic receptor 3) and MYLK (myosin light-chain kinase) (joint P=0.0002), an interaction between two phospholipase C-? isoforms, PLC?1 and PLC?4 (joint P=0.0098), and a modest interaction between ACTN1 (actinin alpha 1) and MYH9 (myosin heavy chain 9) (joint P=0.0326), all localized to calcium-signaled cytoskeletal regulation. Furthermore, we discover a main effect (joint P=5.2E-5) previously unidentified by single-locus analysis within another related gene, SCIN (scinderin), a calcium-binding cytoskeleton regulatory protein. This work illustrates that knowledge-driven interaction analysis of GWAS data is a feasible approach to identify new genetic effects. The results of this study are among the first gene-gene interactions and non-immune susceptibility loci for MS. Further, the implicated genes cluster within inter-related biological mechanisms that suggest a neurodegenerative component to MS.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Neurologie > Neuroimmunologie (Kappos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Neurologie > Neuroimmunologie (Kappos)
UniBasel Contributors:Kappos, Ludwig
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publ. Group
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:06 Dec 2013 09:36
Deposited On:06 Dec 2013 09:36

Repository Staff Only: item control page