The WPA Section on Genetics in Psychiatry: scientific progress and clinical translation

The WPA Section on Genetics in Psychiatry focuses primarily on the role of genetics in the etiology and treatment of psychiatric disorders, with a particular interest in translating these findings to the clinic. The members of the Section are a mixture of active clinicians and researchers, many of whom are also regular members of the International Society of Psychiatric Genetics. Compared to that larger Society, the WPA Section is more focused on potential uses of genetics in clinical settings and on cultivating a global diverse community consistent with the goals of the broader WPA parent organization ¹ .

The Section meets every month to discuss clinically relevant topics and provide a global link between scientists, people with lived experience, and other mental health practitioners. As part of its mandate to promote the growth of a community of clinically oriented scientists and clinicians, the Section has organized several symposia and courses at WPA congresses across three continents (in Thailand, Malta, India, United Arab Emirates, Poland, Austria and Mexico) to inform local scientists and clinicians about recent advances in psychiatric genetics, with an emphasis on how these can be translated into their clinical practice. In preparation for the 2023 World Congress of Psychiatry in Vienna, the Section published an educational booklet to inform clinicians about psychiatric genetics and the potential value of pharmacogenetic testing ² .

Over the past decade, scientific progress has greatly advanced our understanding of how both common and rare genetic variations contribute to the etiology of major psychiatric disorders, including schizophrenia, bipolar disorder and major depression. Strong evidence now indicates that disease risk is influenced by hundreds, potentially thousands, of common alleles with small effect sizes that likely make up the bulk of the genetic risk. Although these small effect sizes pose challenges for study, they can be aggregated into polygenic risk scores, which are increasingly explored in clinical research as potential predictors of psychopathology and treatment response. Genome‐wide association studies (GWAS) of almost all major psychiatric disorders have now identified tens to hundreds of significant loci ³ . The main challenge facing the field is how to progress from statistical associations to a biological understanding of how risk gives rise to the pathophysiology experienced by our patients.

With the advent of high‐throughput and increasingly cost‐effective means of performing whole exome and whole genome sequencing, large‐scale sequencing studies are now increasingly being performed, with a main focus on novel variant discovery ⁴ , ⁵ . Rare variants offer a distinct advantage by potentially pinpointing specific genes (rather than broader loci identified by GWAS) and revealing the direction of effect. While these studies are just beginning to uncover these variants, efforts are underway worldwide to increase sample size and diversity in order to enhance efforts for equitable discovery.

One specific type of rare variants already used in clinical practice includes rare duplications or deletions known as copy‐number variants (CNVs). These variants are often pleiotropic (i.e., associated with a range of phenotypes), but are particularly relevant in the study of intellectual disability and severe autism spectrum disorders. The clinical relevance of CNV testing for neurodevelopmental disorders in children has been recently reviewed ⁶ , and surveys are being conducted to evaluate the knowledge of best practices among professionals.

Another major focus of the Section is the potential of pharmacogenetics to improve clinical care. There is now robust evidence that variations in drug‐metabolizing enzymes (in particular CYP2C19 and CYP2D6) are associated with levels of several antidepressant and antipsychotic medications. However, the role of such variation in clinical response and overall tolerability needs to be explored in larger, more diverse studies across the world. Our Section is therefore proud to be participating in the PSY‐PGx project ⁷ , a global non‐industry‐sponsored study funded by the European Union Horizon 2020 initiative that will test the effectiveness of pharmacogenetic testing in a broad range of psychiatric disorders.

A key priority of the Section is advancing diversity and inclusion in genetic research by fostering the inclusion of a broader range of populations. Ethically, it is essential to address health disparities by ensuring that the various populations are adequately represented. Scientifically, incorporating more diverse populations in GWAS can lead to a more comprehensive understanding of the genetic architecture of psychiatric disorders, and can improve the accuracy of polygenic risk scores. In pharmacogenomics, research has shown that actionable alleles vary significantly across populations, highlighting the need for more trans‐ancestry studies. So, this approach is crucial not only for ethical reasons of equality, inclusion and representation, but also for advancing scientific discovery and enhancing clinical applications.

Finally, we aim to ensure that research and implementation in psychiatric genetics also address critical topics such as social justice, stigma reduction, autonomous decision‐making, the right to know or not know, and data protection. The WPA provides an ideal platform to evaluate, discuss and monitor these issues globally, bringing together diverse perspectives that matter to those living with psychiatric disorders. We enthusiastically invite scientists, clinicians and patients who share these goals to join us in this endeavor.