Population-based gene discovery in psychiatric diseases

There is strong evidence that psychiatric disorders, such as schizophrenia and bipolar, have a significant genetic component. Yet, despite many attempts, the susceptibility genes that predispose to these illnesses have not been revealed. We describe an approach to the discovery of genes involved in such complex diseases. The prospect of gene discovery is optimized by considering elements, such as the applicability of a family- versus population-based paradigm, sample size and use of an isolated population. We suggest that a high level of statistical significance can be achieved by efficient scanning of a dense map of polymorphisms followed by intensive genotyping of informative variations and haplotype analysis.