Genome-wide association study of delay discounting in 134,935 individuals identifies novel loci and transdiagnostic associations across mental and physical health

Abstract

Delay discounting (DD), a persons preference for smaller immediate rewards over larger delayed rewards, is a heritable trait that is associated with psychiatric and physical outcomes, yet the biological mechanisms underlying these links are not known. We performed a GWAS of DD using 134,935 adults and identified 14 genome-wide significant loci. We observed genetic correlations between DD and 73 behavioral, physical, and neuroimaging traits, many of which persisted even after accounting for educational attainment, intelligence, and executive function. Network analysis revealed that the associations between DD and certain traits were explained by both overlapping and trait-specific biological processes. In a hospital-based cohort (N = 66,917), DD polygenic scores were associated with 212 medical conditions. These results demonstrate that DD has a pleiotropic and polygenic common variant architecture, and is genetically associated with numerous outcomes, making it a promising endophenotype for psychiatric and physical health.