Expression-based Polygenic Risk Score Workshop
Led by the Ludmer Centre, the ePRS Workshop is a joint collaboration with the McGill Seminar Series in Quantitative Life Sciences & Medicine and the Canadian Open Neuroscience Platform (CONP).
Who should attend: Researchers and trainees, globally, who plan to or are considering applying Polygenetic Risk Scores (PRS) to their data and want to learn more about a novel, but proven biological-informed, expression-based Polygenetic Risk Scores (ePRS). This multimodal ePRS approach moves beyond the analysis of single genes, found in classical PRS methods, to enable researchers to associate a gene network with behavioural and brain imaging phenotypes.
Participants will learn the differences between the various types of polygenic scores, and how co-expression networks are used to create expression-based PRSs.
To receive background materials and Zoom link:
Register via Eventbrite – click here.
3 November 2020 — 12:00 to 2:30pm — Program
- 12:00-1:00 pm, Method Lecture: Deriving biologically-informed, expression-based Polygenic Risk Scores (ePRS)
- 1:00-1:15 pm: Break to get your lunch and a coffee
- 1:15-1:30 pm Lunch session: Introduction to the free CONP resources, where you can download the ePRS-5HTT and other open-source tools and open-science datasets.
- 1:30-2:30 pm, ePRS-5-HTT Tutorial: What is a brain-region-specific expression-based polygenic score? Calculating the amygdala-based 5HTT ePRS in your data.
Guest Speaker: Patricia Pelufo Silveira MD, MSc, PhD
Dr Silveira is an Assistant Professor in the Department of Psychiatry at McGill University, leads the Environmental Adversity, Neurodevelopment and Mental Health theme-based group at the Douglas Mental Health University Institute, and is the Scientific Director (Int) of the Genomic & Epigenetics Pillar at the Ludmer Centre for Neuroinformatics & Mental Health.
QLS&M Lecture, 12:00-1:00
Deriving biologically-informed, expression-based Polygenic Risk Scores (ePRS)
Abstract: Genome-wide association studies (GWASs) confirm brain disorders are complex polygenic disorders. While never designed to identify the multiple genetic and environmental (epigenetic) interactions that lead to brain disorders, GWASs hold a wealth of underexploited data that could do this. Evolving Polygenic Risk Score (PRS) methods offer the greatest potential to exploit GWAS technology to understand these epigenetic effects. Dr PP Silveira has developed a novel, but proven, methodology for deriving biologically-informed, expression-based PRSs (ePRS)1 using gene co-expression networks to decrypt the pathophysiology and elucidate these neurobiological mechanisms.
- ePRS Methodology: S.A. Hari Dass, et al. PP Silveira. A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions. EBioMedicine, 42 (2019), pp. 188-202
In addition to its unique focus on networks and the region/tissue specificity, the strength of the ePRS method derives from the triangulation of data from multiple types of data-collection methods and omics datasets. This not only captures different dimensions of the same phenomenon but also serves to cross-validate the data and the results. It also involves at least 3 different datasets/samples. One to establish the co-expression network (mice or human postmortem data), another to filter for the specific developmental expression pattern to select the genes that are over-expressed in a certain developmental period, the sample to map SNP to gene expression, and the target cohort (the requesting researcher’s data). Conceptually, each score is a puzzle piece; the completed puzzle is the ePRS. Finally, each ePRS is replicated in a separate cohort, the gold standard for scientific research.
Each ePRS produced using this methodology contributes to a much-needed library of functional genomics scores tracing dynamic neurobiological mechanisms to inform basic, pharmacological and clinic research, with potential application as diagnostic and prognostic tools.
Registered participants will receive a list of ePRS publications to date.
CONP Tutorial, 1:30-2:30 pm
What is a brain-region-specific expression-based polygenic score? Calculating the amygdala-based 5HTT ePRS in your data.
Participants will learn concepts of classical versus expression-based polygenic scores and, as an example, guided to apply an ePRS specifically designed to reflect variations in gene expression of the serotonin-transporter-gene network (5-HTT) in the amygdala, the ePRS-5HTT tool, to different population samples with genotype data.
ePRS-5-HTT tool: As reported in the ePRS-5HTT publication, the amygdala 5-HTT gene network ePRS was used in samples from children to identify individual behavioural differences in response to exposure to early life adversity. The study’s findings provide strong evidence that serotonin and its transporter function are important contributors to heterogeneity, and may associate with increased risk for psychopathology later in life. The results suggest that the 5-HTT-ePRS is a strong predictor of attention-related processes and a linked between severity and the quality of the early-childhood environment, lending support for early interventions. As proven diagnostic tool, the 5-HTT-ePRS tool could enable early identification of those children with ADHD in need of intervention.
Resources: The ePRS-5-HTT tool is being containerize for inclusion on the Canadian Open Neuroscience Platform (CONP). Registered participants will receive the URL to download the ePRS-HTT and related materials.
McGill’s Quantitative Life Sciences (QLS) PHD program, the Centre for Applied Mathematics in Bioscience and Medicine (CAMBAM), the McGill initiative in Computational Medicine (MiCM), and the Ludmer Center for Neuroinformatics & Mental Health have join forces to offer weekly interdisciplinary seminars. The tutorial was developed in collaboration with the Canadian Open Neuroscience Platform (CONP).