Abstract

Delay discounting (DD), the tendency to discount the value of delayed versus current rewards, is elevated in a constellation of diseases and behavioral conditions. We performed a genome-wide association study of DD using 23,127 research participants of European ancestry. The most significantly associated single-nucleotide polymorphism was rs6528024 (P = 2.40 × 10−8), which is located in an intron of the gene GPM6B. We also showed that 12% of the variance in DD was accounted for by genotype and that the genetic signature of DD overlapped with attention-deficit/hyperactivity disorder, schizophrenia, major depression, smoking, personality, cognition and body weight.

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Acknowledgements

We thank the research participants and employees of 23andMe for making this work possible. J.M. was partially supported by the Peter Boris Chair in Addictions Research. S.S.-R. was supported by the Frontiers of Innovation Scholars Program (FISP; #3-P3029), the Interdisciplinary Research Fellowship in NeuroAIDS (IRFN; MH081482) and a pilot award from DA037844.

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Author notes

  1. A full list of members appears in the Supplementary Note

  2. A full list of members appears in the Supplementary Note.

Affiliations

  1. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA

    • Sandra Sanchez-Roige
    •  & Abraham A. Palmer
  2. 23andMe, Inc., Mountain View, CA, USA

    • Pierre Fontanillas
    •  & Sarah L. Elson
  3. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA

    • Anita Pandit
    • , Ellen M. Schmidt
    •  & Gonçalo R. Abecasis
  4. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway

    • Johanna R. Foerster
  5. Center for Deployment Psychology, Uniformed Services University, Bethesda, MD, USA

    • Joshua C. Gray
  6. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA

    • Harriet de Wit
  7. Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA

    • Lea K. Davis
  8. Peter Boris Centre for Addictions Research, McMaster University/St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada

    • James MacKillop
  9. Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA

    • Abraham A. Palmer

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Consortia

  1. the 23andMe Research Team

    Contributions

    Conceptualization: A.A.P., J.M.; analysis and software: S.S.-R., P.F., L.K.D., J.C.G., A.A.P.; writing: S.S.-R., A.A.P.; review and editing: all authors.

    Competing interests

    P.F., S.L.E., and members of the 23andMe Research Team are employees of 23andMe Inc. The opinions and assertions expressed herein are those of the authors; specifically, with respect to J.C.G., they do not reflect the official policy or position of the Uniformed Services University or the Department of Defense.

    Corresponding author

    Correspondence to Abraham A. Palmer.

    Integrated Supplementary Information

    1. Supplementary Figure 1 Regional association plot focusing on top SNP rs6528025 at 3′ of GPM6B gene on chromosome X at position 13.9 Mb

      This plot was generated using LocusZoom1. The -log10(P value) is shown on the left y-axis; position in Mb is on the x-axis. Recombination rates (expressed in centiMorgans cM per Mb; NCBI Build GRCh37; highlighted in blue) are shown on the right y-axis. Pairwise linkage disequilibrium (r2) of each SNP with the top SNP in the region is indicated by its color. Crossed points represent imputed SNPs, circles represent directly genotyped SNPs. The statistical tests used were two-sided; sample size = 23,217.

    2. Supplementary Figure 2 Regional association plot showing the second index SNP rs2665993, located in the EVPL gene on chromosome 17

      This plot was generated using LocusZoom1. The -log10(P value) is shown on the left y-axis; position in Mb is on the x-axis. Recombination rates (expressed in centiMorgans cM per Mb; NCBI Build GRCh37; highlighted in blue) are shown on the right y-axis. Pairwise linkage disequilibrium (r2) of each SNP with the top SNP in the region is indicated by its color. Crossed points represent imputed SNPs, circles represent directly genotyped SNPs. The statistical tests used were two-sided; sample size = 23,217.

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    DOI

    https://doi.org/10.1038/s41593-017-0032-x