Complex gene-gene interactions in multiple sclerosis: A multifactorial approach reveals associations with inflammatory genes

Alison A. Motsinger, David Brassat, Stacy J. Caillier, Henry A. Erlich, Karen Walker, Lori L. Steiner, Lisa F. Barcellos, Margaret A. Pericak-Vance, Silke Schmidt, Simon Gregory, Stephen L. Hauser, Jonathan L. Haines, Jorge R. Oksenberg, Marylyn D. Ritchie

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The complex inheritance involved in multiple sclerosis (MS) risk has been extensively investigated, but our understanding of MS genetics remains rudimentary. In this study, we explore 51 single nucleotide polymorphisms (SNPs) in 36 candidate genes from the inflammatory pathway and test for gene-gene interactions using complementary case-control, discordant sibling pair, and trio family study designs. We used a sample of 421 carefully diagnosed MS cases and 96 unrelated, healthy controls; discordant sibling pairs from 146 multiplex families; and 275 trio families. We used multifactor dimensionality reduction to explore gene-gene interactions. Based on our analyses, we have identified several statistically significant models including both main effect models and two-locus, three-locus, and four-locus epistasis models that predict MS disease risk with between ∼61% and 85% accuracy. These results suggest that significant epistasis, or gene-gene interactions, may exist even in the absence of statistically significant individual main effects.

Original languageEnglish (US)
Pages (from-to)11-20
Number of pages10
JournalNeurogenetics
Volume8
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Epistasis
  • Multifactor dimensionality reduction
  • Multiple sclerosis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

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    Motsinger, A. A., Brassat, D., Caillier, S. J., Erlich, H. A., Walker, K., Steiner, L. L., Barcellos, L. F., Pericak-Vance, M. A., Schmidt, S., Gregory, S., Hauser, S. L., Haines, J. L., Oksenberg, J. R., & Ritchie, M. D. (2007). Complex gene-gene interactions in multiple sclerosis: A multifactorial approach reveals associations with inflammatory genes. Neurogenetics, 8(1), 11-20. https://doi.org/10.1007/s10048-006-0058-9