Multifactor dimensionality reduction reveals gene-gene interactions associated with multiple sclerosis susceptibility in African Americans.

Genes and Immunity
David BrassatMarylyn D Ritchie

Abstract

Multiple sclerosis (MS) is a common disease of the central nervous system characterized by inflammation, myelin loss, gliosis, varying degrees of axonal pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits many of the characteristics that distinguish complex genetic disorders including polygenic inheritance and environmental exposure risks. Here, we used a highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory pathways to explore gene-gene interactions and disease susceptibility in a well-characterized African-American case-control MS data set. We applied the multifactor dimensionality reduction (MDR) test to detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R), IL5RA(-80), CD14(-260)- locus association models that predict MS risk with 75-76% accuracy (P<0.01). These results demonstrate the importance of exploring both main effects and gene-gene interactions in the study of complex diseases.

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Citations

Dec 24, 2009·European Journal of Human Genetics : EJHG·Qianqian PengFuzhong Xue
Jun 22, 2010·Annals of Human Genetics·Stacey J Winham, Alison A Motsinger-Reif
Jul 24, 2010·BMC Bioinformatics·Stacey J WinhamAlison A Motsinger-Reif
Aug 3, 2012·Drug and Alcohol Dependence·R H C PalmerV S Knopik
Jun 19, 2008·Genetic Epidemiology·Alison A Motsinger-ReifMarylyn D Ritchie
Jun 29, 2006·Nature Genetics·John A Todd
Aug 11, 2007·International Journal of Cancer. Journal International Du Cancer·Emma L IvanssonUlf B Gyllensten
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Jul 21, 2006·American Journal of Physiology. Cell Physiology·Nancy E SchlickJozef Lazar
Jan 25, 2013·Genomics & Informatics·Sungyoung LeeTaesung Park
Apr 4, 2021·International Journal of Environmental Research and Public Health·Farren B S Briggs, Corriene Sept

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