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. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology. Precision medicine strives to reclassify complex heterogeneous diseases into distinct biologically defined groups, thereby enabling targeted therapies and improved outcomes. Examples include the subdivision of common cancers by somatic driver mutations 1 , the discovery of eosinophilic variants of asthma 2 and the recognition that some presentations of heart failure may arise from the accumulation of amyloidogenic proteins, which can be subdivided further based on the aggregating protein 3. The realization of precision medicine has