Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.
Navigating the Landscape of Translational Geroscience in Canada: A Comprehensive Evaluation of Current Progress and Future Directions
Abstract The inaugural Canadian Conferences on Translational Geroscience were held as 2 complementary sessions in October and November 2023. The conferences explored the profound interplay between the biology of aging, social determinants of health, the potential societal impact of geroscience, and the maintenance of health in aging individuals. Although topics such as cellular senescence, molecular and genetic determinants of aging, and prevention of chronic disease were addressed, the conferences went on to emphasize practical applications for enhancing older people’s quality of life. This article summarizes the proceeding and underscores the synergy between clinical and fundamental studies. Future directions highlight national and global collaborations and the crucial integration of early-career investigators. This work charts a course for a national framework for continued innovation and advancement in translational geroscience in Canada.