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Krasnow Institute > Monday
Seminars > Abstracts
Genetics and Epigenetics
of
Neuropsychiatric Disorders
Robert Lipsky
Director, Neuroscience Research, Department of Neurosciences, Inova Health System
and Krasnow Institute, GMU
Family, twin, and adoption studies all support a substantial genetic component in susceptibility to neuropsychiatric disorders. Heritability estimates range from 40-100%. Despite all of this evidence, identifying specific genetic variations that influence susceptibility has been difficult. We and others have used a candidate gene approach to identify functional single nucleotide polymorphisms (SNPs) that play a role in susceptibility to a number of these disorders. The effect of these variants on overall risk is modest, consistent with the idea that the genetic contribution to neuropsychiatric disorders is polygenic. Recently, the development of genome-wide association study (GWAS) designs and analysis methods have made it possible to search for multiple genetic variations underlying a condition without knowledge about gene function or genomic regions that might harbor susceptibility variants (so-called “hypothesis free” scans). A number of genetic variations have been discovered to be associated with different traits and diseases.
Other factors act on the genome to produce a phenotype, which is accomplished by the epigenome. Two major epigenetic mechanisms acting on genes are chromatin modification and DNA methylation, which act during cellular differentiation but also respond to the environment. The responsiveness of the epigenome to environmental change has short and long term effects on behavior in normal functioning of the brain and in disease. I will discuss the molecular basis of gene-by-environment effects on neuropsychiatric disorders from the perspective of identifying new targets for therapy.
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