Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health

Delay discounting (DD), a person's 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 23andMe research participants and identified 11 genome-wide significant loci. We did not replicate our previously reported association with rs6528024 (chrXq13.3, GPM6B; P = 5.30 × 10<sup>-02</sup>). The SNP-heritability of DD was 9.85 ± 0.57%. 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.

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Journal
Molecular Psychiatry
Published
2025-11-25
DOI
https://doi.org/10.1038/s41380-025-03356-8
Citations
1
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
1.82

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article

Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health

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Molecular Psychiatry
Genetic Associations and Epidemiology
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Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health

Maria Niarchou, Jared O’Connell, Will Freyman, Aly A. Khan, John J. Meredith, Ethan M. Jewett, Renata B. Cupertino, Anjali J. Shastri, G. David Poznik, Mariela Jennings, Keaton Stagaman, Tiffany A. Greenwood, Shubham Saini, Hayley H. A. Thorpe, Teague Sterling, Sandra Sanchez‐Roige, Meghan E. Moreno, Abraham A. Palmer, Morgan Schumacher, Stella Aslibekyan, Jingchunzi Shi, Steven J. Micheletti, Harriet de Wit, Michał Kmiecik, Sevim B. Bianchi, Yunxuan Jiang, Lea K. Davis, Travis T. Mallard, Dominique T. Nguyen, Adam Auton, Daniel E. Gustavson, Sarah L. Elson, Julie M. Granka, Barry Hicks, Chris Eijsbouts, David A. Hinds, Chris German, Laura Vilar‐Ribó, Alan Kwong, Xin Wang, M. Reza Jabalameli, Katelyn Kukar, Pierre Fontanillas, Ninad S. Chaudhary, Joyce Y. Tung, Priyanka Nandakumar, Payam Dibaeinia, Davide Foletti, Éadaoin Harney, Alejandro Hernandez, Amy Lavin Williams, Alexandra Reynoso, Catherine H. Weldon, Peter Wilton, Teresa Filshtein, Steve Pitts, Jessica Bielenberg, Yanyu Liang, Elizabeth Babalola, Qiaojuan Jane Su, Suyash Shringarpure, Trey Ideker, Leah Selcer, Emily DelloRusso, Sotiris Karagounis, Wei Wang, Sayantan Das, Nicholas Eriksson, James MacKillop, Zach Fuller, Robert K. Bell, Lucy Kaufmann, Bianca A. Llamas, Susana A. Tat, Keng-Han Lin, Shreya R. Pakala, Jane Yang, Vinh Tran, Matthew H. McIntyre, Zayn Cochinwala
article en
1 citations

Abstract

Delay discounting (DD), a person's 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 23andMe research participants and identified 11 genome-wide significant loci. We did not replicate our previously reported association with rs6528024 (chrXq13.3, GPM6B; P = 5.30 × 10<sup>-02</sup>). The SNP-heritability of DD was 9.85 ± 0.57%. 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.

Molecular PsychiatryVol. 31(4)
Western University (CA), Harvard University (US), University of Colorado Boulder (US), University of California San Diego (US), University of Chicago (US), Massachusetts General Hospital (US), 23andMe (United States) (US), La Jolla Bioengineering Institute (US), New York Genome Center (US), St. Joseph’s Healthcare Hamilton (CA), Vanderbilt University Medical Center (US), McMaster University (CA), Icahn School of Medicine at Mount Sinai (US)
Vanderbilt University, Vanderbilt University Medical Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Canadian Institutes of Health Research, National Institute of Mental Health, National Institute on Drug Abuse, National Center for Research Resources, National Center for Advancing Translational Sciences
Openalex Percentile: Top 11%
Genetic Associations and Epidemiology
1.82
DOIOpen Access PDFOpenAlex
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