Toronto, Ontario

Interrogating the Shared Genetics A Multi-phenotype and Cross-locus Colocalization Framework (Proposal Presentation)

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Presenter: Hua (Henry) Lu

Supervisory Committee: Lisa Strug (Supervisor), Rae Yeung (Co-Supervisor), and Shelley Bull

Date and Time: Wednesday, May 1, 2024, 2-4pm EST

Location: 155 College Street, Health Science Building, Room 734

Abstract: Unraveling the shared genetic architectures of phenotypically similar diseases is an important research area in human genetics with important implications for understanding pathobiology and potential treatment implications. The emergence of Multisystem Inflammatory Syndrome in Children (MIS-C) during the COVID-19 pandemic underscores the value of genetic insights for enhancing diagnostics and therapies. MIS-C shares symptoms with immune-mediated conditions such as Kawasaki Disease (KD) and systemic juvenile idiopathic arthritis (sJIA), motivating methodologies that assess shared genetics across diseases and -omic features. Traditional Polygenic Risk Scores (PRS), which summarize genetic predispositions from Genome-Wide Association Studies (GWAS), are crucial for examining genetic overlaps but do not target specific loci. In contrast, colocalization analysis identifies shared genetics at specific loci but is generally limited to one locus at a time and presents challenges in multi-trait analysis. This leads interest in extending our existing Simple Sum 2 (SS2) colocalization procedure to multi-phenotype and cross-loci analyses, providing a flexible and integrated way to explore shared genetic mechanisms across traits. Therefore, my thesis aims to 1) Develop a multi-phenotype statistical colocalization framework based on our Simple Sum 2 (SS2) methodology, applying it to assess shared loci between MIS-C and other immunophenotypes and molecular QTLs. 2) Extend colocalization procedures to genome-wide analysis by integrating the colocalization across multiple loci. Incorporate the multi-phenotype and cross-locus functionality into the current LocusFocus software. 3) Compare the extended colocalization procedure with conventional PRS to evaluate the shared genetic contributions between MIS-C and other immunophenotypes

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