background Psychiatric genetics is, as a field, advancing rapidly in several directions. There is a need to provide an overall coherent view of the field and how the different research paradigms relate to each other with their relatives strengths and weaknesses.
aim To provide an overview of the field of psychiatric genetics.
summary The talk will begin with an elaboration of the four major paradigms in psychiatric genetics: simple genetic epidemiology, advanced genetic epidemiology, gene-finding methods, and molecular biology. The strengths and limitations of each of these methods will be outlined, as well as their interrelationships. Then, pertinent illustrations will be provided for the first three paradigms. We will review the heritability of the major psychiatric disorders. We will then review a selected set of findings from advanced genetic epidemiology. These will include: i) multivariate modeling that examines the role of genes in explaining the patterns of comorbidity in psychiatric disorders, ii) adding time into genetic models to clarify the developmentally dynamic nature of gene action in psychiatric illness, iii) genotype-environment interaction and iv) genotype-environment correlation. Examples will be provided of integrated etiologic models incorporating multiple environmental risk factors into genetically informative designs. The section on gene-finding methods will begin with a brief review of association and linkage methodologies as applied to complex traits. We will discuss the conceptual issue of what it means to have a “gene for” a disorder. This discussion will conclude that such phraseology, although commonly used in the professional and lay literature, is probably inappropriate for genetic influences on psychiatric illness. We will then review briefly linkage and candidate gene association results. Then, we will examine the new major paradigms in gene-finding methods - genome wide association studies (gwas) and copy number variants. Summary results will be presented from the schizophrenia work group of the Psychiatric gwas Consortium. The talk will conclude with a discussion of the role of bio-informatics and new polygene methods for analyzing gwas results.
conclusion Psychiatric genetics is a dynamic field moving down toward molecular mechanisms and out into the environment using genetic epidemiological tools. Both approaches are of value and will ultimately complement each other.