Genetic Studies of Psychiatric Disorders: The Basic Concepts and Methods of Quantitative Genetics

Joo, Eun Jeong; Kim, Yong Sik

Abstract

Quantitative medical genetics including genetic epidemiological studies, linkage studies, and association studies are the basis for molecular genetic studies to find the susceptible genes or responsible mutations for psychiatric disorders. Epidemiological studies on recurrence risk, twin studies and adoption studies have shown that genetic components are contributing for the development of psychiatric disorders. The basic concept of quantitative genetics is recombination and linkage phenomenon. Linkage is that two genetic loci located close enough to each other will not be separated after recombination in meiosis. Linkage analysis and association studies can be accomplished by appropriate genetic analysis methods with genetically well defined phenotype data and genotype data generated by PCR. Linkage analysis are focused on simultaneous transmission of genotype and phenotype in multiplex pedigrees. Linkage analysis could be divided into two categories: parametric and nonparametric methods. Association studies are designed to find linkage disequilibrium between candidate gene and disease phenotype. Family-based association study methods are recommended to exclude possible population stratification of population-based case control studies. In spite of lots of evidence supporting great genetic influence on psychiatric disorders, genetic studies on psychiatric disorders have not been easy. It is probably because psychiatric disorders are composed of complex traits which do not follow Mendelian inheritance and several genes may contribute to only a small proportion of variances in the trait. In order to solve this complexity, animal models and genetically proper endophenotypes should be developed and be applied to QTL (Quantitative Trait Loci) analysis. At the same time, statistically powerful sample size should be established through worldwide collaboration to overcome small gene effects of psychiatric disorders.