Genetics in psychiatry: are the promises met?

ABSTRACT

OBJECTIVES: Psychiatric disorders are among the most heritable common disorders, and for more than 20 years researchers have tried to unravel genetic susceptibility genes. This review briefly outlines the pros and cons of genetic approaches, important advances and possible future directions for readers not familiar with genetic studies. METHODS: In this article the results of 20 years molecular genetics in psychiatry are shortly and critically summarized on the basis of important reviews and meta-analyses of the last decade, without describing and enumerating the different findings (see special reviews). RESULTS: Conventional linkage and candidate association studies revealed numerous, but also inconsistent and sometimes contradictory results. The reasons are assumed to include the complexity of the disorder with interaction of several genes of small effects, lack of a valid phenotype, and invalid statistical and methodological issues. Recent systematic genome-wide association studies (GWAS) have reported association of some common variants for schizophrenia and bipolar disorder. However, the risk conferred by these variants is small and genome-wide significance is rare. Also structural variations might be important, and interesting data are arising from copy-number-variations (CNVs). CONCLUSIONS: Although the new data from GWAS are promising, they still do not meet our initial expectations, identifying a "susceptibility gene". However, they opened new aspects concerning aetiology of psychoses, and the incorporation of new approaches, as epigenetics, or gene-environment interaction, is needed in future study designs.