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Updated: Apr 20, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Epistasis in the risk of human neuropsychiatric disease
1Department of Genetics, Institute of Quantitative Biomedical Sciences, Geisel School of Medicine, Dartmouth College, 78 College ST, HB 6044, Hanover, NH, 03755, USA, scott.williams@dartmouth.edu.
Abstract:
Neuropsychiatric disease represents the ideal class of disease to assess the role of epistasis, as more genes are expressed in the brain than in any other tissue. In this chapter, two well-studied neuropsychiatric diseases are examined, Alzheimer's disease (AD) and schizophrenia, which have been shown to have multiple and, often, replicated interactions that associate with clinical endpoints or related phenotypes. In each case, a single gene is represented in a plurality of epistatic interactions, apolipoprotein E (APOE) for AD and catechol-O-methyltransferase for schizophrenia. Interestingly, of the two, only APOE has clear-cut and consistent evidence for a marginal association. Unraveling the underlying reasons is important in understanding both genetic etiology and architecture as well as how to use genetics to provide better personalized treatments.
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