Advances in our understanding of the genetic contributions to mental illness - David Curtis UGI

Three papers published in Nature Genetics and Nature report novel findings which significantly impact understanding of the ways in which genetic variation can affect the risk of developing serious mental illness. In an accompanying editorial in the British Journal of Psychiatry, David Curtis of the UCL Genetics Institute, who is a co-author of the papers, describes the implications for psychiatrists in terms of their understanding of mental illness in general and of schizophrenia in particular.

The first paper, published in Nature Genetics, reports that variants damaging the functioning of the AKAP11 gene substantially increase the risk of developing either bipolar disorder or schizophrenia. This is the first specific gene to be implicated in bipolar disorder risk.

The second paper, published in Nature, reports the latest genome-wide association study of schizophrenia and identifies 287 genomic loci at which variation influences schizophrenia risk, with the effects being concentrated at loci implicated in neuronal function, including synaptic organization, differentiation and transmission.

The third paper, also published in Nature, reports the results from a large exome-sequencing study of schizophrenia. It implicates ten specific genes in which very rare variants damaging gene function substantially increase risk of developing schizophrenia. As discussed in the editorial in the British Journal of Psychiatry, these results provide a concrete demonstration of how impaired biological function can lead to mental illness. The findings will allow scientists to use model systems to explore the effects of disturbed functioning of these genes in order to gain a better understanding of the mechanism involved in mental illness and, ultimately, in order to devise improved treatments.

Curtis D. Identification of specific genes involved in schizophrenia aetiology – what difference does it make? The British Journal of Psychiatry 2022 https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/identification-of-specific-genes-involved-in-schizophrenia-aetiology-what-difference-does-it-make/9E78768FDBC5B19D2A921DF541F54429#

Palmer P and the Bipolar Exome Sequencing Collaboration. Exome sequencing in bipolar disorder reveals AKAP11 as a risk gene shared with schizophrenia. Nature Genetics 2022 http://dx.doi.org/10.1038/s41588-022-01034-x

Trubetskoy V and the Schizophrenia Working Group of the Psychiatric Genetics Consortium. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 2022 https://doi.org/10.1038/s41586-022-04434-5

Singh T and the Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA) consortium. Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature 2022 https://doi.org/10.1038/s41586-022-04556-w