Scholarlink

<p>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, <i>GPM6B</i>; <i>P</i> = 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 (<i>N</i> = 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月25日

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

摘要

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 × 10−02). 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.