Poster Presentation GENEMAPPERS 2024

Leveraging pleiotropy for the improved treatment of psychiatric disorders (#82)

Damian J Woodward 1 2 , Jackson G Thorp 1 3 , Christel M Middledorp 4 5 6 7 8 , Wole Akosile 9 , Eske M Derks 1 , Zachary F Gerring 1 10
  1. Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  2. Queensland University of Technology, Brisbane, QLD, Australia
  3. School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
  4. Department of child and adolescent psychiatry and psychology, Amsterdam UMC, Amsterdam, The Netherlands
  5. Arkin Mental Health Care, Amsterdam, The Netherlands
  6. Levvel Academic Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands
  7. Child Health Research Centre, University of Queensland, Brisbane, Australia
  8. Child and Youth Mental Health Service, Children’s Health Queensland Hospital and Health Service, Brisbane, Australia
  9. Greater Brisbane Clinical School, University of Queensland, Brisbane, Australia
  10. Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

Over 90% of drug candidates fail in clinical trials, while it takes 10-15 years and 1 billion US dollars to develop one successful drug. Drug innovation is especially poor for psychiatric disorders, where a lack of objective biomarkers for psychiatric diagnoses and the assessment of treatment outcomes contributes to clinical trial failure. In addition, disease comorbidity and complex symptom profiles among psychiatric disorders obscure the identification of causal mechanisms for therapeutic intervention. Therefore, new approaches are urgently needed to identify more suitable drug candidates for clinical trials. One approach is integrating human genetic data into the drug candidate selection process. Genome-wide association studies have identified thousands of replicable risk loci for psychiatric disorders, and sophisticated statistical tools are increasingly effective at using these data to pinpoint likely causal genes. These studies have also uncovered shared or pleiotropic genetic risk factors underlying comorbid psychiatric disorders. The study of shared genetic effects between psychiatric disorders may provide new opportunities for novel therapeutics that target a common mechanism rather than treating each disease separately. In this article, we argue that leveraging pleiotropic effects will provide opportunities for the discovery of novel drug targets and facilitate the identification of more effective treatments for psychiatric disorders.