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

Genes & Immunity volume 7, pages 310–315 (2006)Cite this article

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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Acknowledgements

We are grateful to the MS patients and their families for participating in this study. We thank R.R. Lincoln, C. DeLoa, R. Harrison, W. Chin, H. Mousavi and R. Guerrero for recruitment of patients to the study, database management, and expert technical help. This work was funded by Grant RG3060 from the National Multiple Sclerosis Society and by National Institutes of Health Grants NS046297, GM31304, AG20135, and in part by HL65962, the Pharmacogenomics of Arrhythmia Therapy U01 site of the Pharmacogenetics Research Network.

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Author notes

  1. D Brassat and A A Motsinger: Both these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Center for Human Genetics, School of Medicine, University of California at San Francisco, San Francisco, CA, USA

    D Brassat, S J Caillier, B A C Cree, S L Hauser & J R Oksenberg

  2. Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA

    A A Motsinger, J L Haines & M D Ritchie

  3. Department of Human Genetics, Roche Molecular Systems, Alameda, CA, USA

    H A Erlich, K Walker & L L Steiner

  4. Division of Epidemiology, School of Public Health, UC Berkeley, Berkeley, CA, USA

    L F Barcellos

  5. Center for Human Genetics, Duke University Medical Center, Durham, NC, USA

    M A Pericak-Vance, S Schmidt & S Gregory

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  1. D Brassat
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Correspondence to M D Ritchie.

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Brassat, D., Motsinger, A., Caillier, S. et al. Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans. Genes Immun 7, 310–315 (2006). https://doi.org/10.1038/sj.gene.6364299

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  • DOI: https://doi.org/10.1038/sj.gene.6364299

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