title: Multifactor dimensionality reduction reveals gene-gene interactions associated with multiple sclerosis susceptibility in African Americans.
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.
authors.affiliation: Department of Neurology and Center for Human Genetics, School of Medicine, University of California at San Francisco, USA.
authors.forename: D
authors.initials: D
authors.lastname: Brassat
authors.forename: A A
authors.initials: AA
authors.lastname: Motsinger
authors.forename: S J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: H A
authors.initials: HA
authors.lastname: Erlich
authors.forename: K
authors.initials: K
authors.lastname: Walker
authors.forename: L L
authors.initials: LL
authors.lastname: Steiner
authors.forename: B A C
authors.initials: BA
authors.lastname: Cree
authors.forename: L F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: S
authors.initials: S
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Gregory
authors.forename: S L
authors.initials: SL
authors.lastname: Hauser
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: M D
authors.initials: MD
authors.lastname: Ritchie
mesh_terms: D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053666:Interleukin-5 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D020412:Multifactorial Inheritance; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*
chemical_list: C485918:IL5RA protein, human; D053666:Interleukin-5 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4