Digital phenotyping from wearables using AI characterizes psychiatric disorders and identifies genetic associations.

Psychiatric disorders are complex and influenced by both genetic and environmental factors. However, studying the full spectrum of these disorders is hindered by practical limitations on measuring human behavior. This highlights the need for novel technologies that can measure behavioral changes at an intermediate level between diagnosis and genotype. Wearable devices are a promising tool in precision medicine, since they can record physiological measurements over time in response to environmental stimuli and do so at low cost and minimal invasiveness. Here we analyzed wearable and genetic data from a cohort of the Adolescent Brain Cognitive Development study. We generated >250 wearable-derived features and used them as intermediate phenotypes in an interpretable AI modeling framework to assign risk scores and classify adolescents with psychiatric disorders. Our model identifies key physiological processes and leverages their temporal patterns to achieve a higher performance than has been previously possible. To investigate how these physiological processes relate to the underlying genetic architecture of psychiatric disorders, we also utilized these intermediate phenotypes in univariate and multivariate GWAS. We identified a total of 29 significant genetic loci and 52 psychiatric-associated genes, including ELFN1 and ADORA3. These results show that wearable-derived continuous features enable a more precise representation of psychiatric disorders and exhibit greater detection power compared to categorical diagnostic labels. In summary, we demonstrate how consumer wearable technology can facilitate dimensional approaches in precision psychiatry and uncover etiological linkages between behavior and genetics.