The high-dimensional space of human diseases built from diagnosis records and mapped to genetic loci

Abstract

AbstractHuman diseases are traditionally studied as singular, independent entities, limiting researchers’ capacity to view human illnesses as dependent states in a complex, homeostatic system. Here, using time-stamped clinical records of over 151 million unique Americans, we construct a disease representation as points in a continuous, high-dimensional space, where diseases with similar etiology and manifestations lie near one another. We use the UK Biobank cohort, with half a million participants, to perform a genome-wide association study of newly defined human quantitative traits reflecting individuals’ health states, corresponding to patient positions in our disease space. We discover 116 genetic associations involving 108 genetic loci and then use ten disease constellations resulting from clustering analysis of diseases in the embedding space, as well as 30 common diseases, to demonstrate that these genetic associations can be used to robustly predict various morbidities.