Max Homilius, Wandi Zhu, Samuel S Eddy, Patrick C Thompson, Huahua Zheng, Caleb N Warren, Chiara G Evans, David D Kim, Lucius L Xuan, Cissy Nsubuga, Zachary Strecker, Christopher J Pettit, Jungwoo Cho, Mikayla N Howie, Alexandra S Thaler, Evan Wilson, Bruce Wollison, Courtney Smith, Julia B Nascimben, Diana N Nascimben, Gabriella M Lunati, Hassan C Folks, Matthew Cupelo, Suriya Sridaran, Carolyn Rheinstein, Taylor McClennen, Shinichi Goto, James G Truslow, Sara Vandenwijngaert, Calum A MacRae, Rahul C Deo
Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases...
December 4, 2023: Nature Genetics