This sequencing project will identify interacting genetic and environmental risk factors for children and youth with mental health disorders, supporting earlier intervention.

Mental health disorders (MHDs) typically begin early in life (75 per cent before the age of 25) affecting an estimated one in five children and youth (1.6 million Canadians). MHDs are highly heritable, and recent research has focused on identifying genetic risk and protective factors to inform effective approaches to risk stratification and targeted interventions. However, multiple barriers remain in realizing the promise of precision medicine in child and youth mental health, including small sample sizes, limited standardization of phenotyping or linkage to “real-world” (e.g. electronic health record, administrative health, patient reported) data and lack of representation from people of non-European ancestry potentially exacerbating existing health care inequities. To address these barriers, we propose a large-scale, collaborative Pan-Canadian initiative to link Genomic, Environmental and Mental Health Data (Pan-GEM) to identify risk factors for MHDs. We will perform short-read whole genome sequencing on 5,250 children and youth and (if funded) long-read whole genome sequencing on 1,200 children and youth. We have assembled a group of investigators from across Canada who have made extensive contributions to diverse fields including psychiatric genetics, pharmacogenetics, data science, and health policy. Members of our team lead 11 large, ongoing cohort studies from which participants will be recruited in Phase 1 of our study. In Phase 2 of our study, we will collect a new, Pan-GEM specific cohort leveraging Phase 1 recruitment but over-sampling people of non-European ancestry. If funded, we will conduct Phase 3 recruitment for long-read sequencing, also over-sampling people of non-European ancestry Pan-GEM will have the following Aims: 1) Build a collaborative, pan-Canadian network of child and youth mental health researchers leveraging existing networks and resources. 2) Develop, validate, and share standardized algorithms, workflows, and analysis plans for combining data. 3) Co-develop culturally sensitive recruitment/retention, consenting, and knowledge translation approaches. 4) Sequence samples and combine phenotype data collected through Pan-GEM, conducting analyses of interactions between social determinants of health and genetic variation. 5) Develop practice guidelines and policy recommendations that address Genomics and its Ethical, Environmental, Economic, Legal and Social aspects (GE³LS) through knowledge translation (KT). Leveraging and amplifying national investments and expertise in mental health genetic research, Pan-GEM will be the largest Canadian collaboration to focus on identifying genetic and environmental risk factors for children and youth with MHDs. By addressing current barriers in the field through this unified approach, and ensuring diverse representation amongst our participants, we will facilitate advances in precision medicine that will benefit all young Canadians.