Van genetische bevindingen naar de klinische praktijk van de psychiater: hoe genetica precisiepsychiatrie mogelijk kan maken

Abstract

BACKGROUND Most psychiatric disorders are characterized by a complex genetic background where many common variants are involved. Nowadays, we are able to ‘read’ these variants, test for their association with phenotypes in genome-wide association studies (gwas), and perform further downstream analyses. However, the impact of such findings on clinical psychiatry has remained largely unclear. AIM To provide new insight into the degree of genetic overlap between psychiatric disorders and neurological disorders. And to investigate how genetic findings may impact clinical practice in psychiatry. METHOD Bioinformatics and statistical methods were applied to perform analyses in large genetic datasets. In particular, we focused on: pathway analyses in schizophrenia; a multivariate gwas of stress and trauma phenotypes; and genetic overlap analyses between amyotrophic lateral sclerosis (als) and schizophrenia. Finally, we assessed for which psychiatric disorders genetic findings are most likely to impact clinical practice in the near future. RESULTS First, we found enrichment of common genetic variants associated with schizophrenia in synaptic signalling pathways relating to dopaminergic, acetylcholinergic and glutamatergic neurons. Second, we found that als and schizophrenia partly share common genetic risk. And third, we outline the clinical relevance of genetic cross-disorder studies in psychiatry, and posit that these studies have meaning for diagnostics, prognostics and treatment prediction in psychiatry. CONCLUSION The summarized and previous genetic studies into psychiatric disorders will hopefully soon enable precision psychiatry, as genetics is a powerful tool to elucidate individualized risk profiles of patients and their responses to psychotropic medication. Genetic counselling allows clinicians to carefully balance the wide range of considerations in those patients and relatives with questions related to genetic underpinnings of disease and treatment response.