UC Berkeley

How do experts stitch together seemingly irreconcilable scientific objects? This paper examines the way “endophenotypes” and “deep phenotyping” are deployed to bridge the infamously recalcitrant genotype–phenotype divide. The endophenotype concept emerged in mid-20th-century evolutionary biology/entomology and was briefly adopted in schizophrenia genetics in 1972 before virtually disappearing for a generation. Decades later, in the “postgenomic” 2000s, the concept exploded in medical—and especially psychiatric—genetics in the United States and United Kingdom. Endophenotypes now refer to phenotypic observations like subclinical biomarkers or traits that are both more fine-grained than disease categories and yield stronger associations with genetics. We argue that the endophenotype concept functions as an “epistemic quilting device” that allows experts to forge research programs across disjunct scientific ontologies and fields, creating new wholes that respond to historically specific needs. But they are also destabilizing existing medical categories and foundational concepts in genetics like penetrance and recessivity, with radical implications for “precision medicine.” Today, endophenotypes and the more loosely defined “deep phenotyping” have been integrated into the infrastructures of postgenomic research in both rare disease and big-data genomics, quilting together genetics and other fields interested in human illness and difference even as it disrupts them.