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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Change history
08 January 2019
The author list was in the wrong order in the HTML version of the original article and in the HTML version of the original correction notice. This has been corrected to show the 23andMe Research Team as the fourth author and Abraham A. Palmer as the last author in both places.
11 May 2018
In the version of this article initially published, the consortium authorship was not presented correctly. The 23andMe Research Team was listed as the last author, rather than the fourth, and a line directing readers to the Supplementary Note for a list of members did appear but was not directly associated with the consortium name. Also, the Supplementary Note description stated that both member names and affiliations were included; in fact, only names are given. Finally, the URL for S-PrediXcan was given in the Methods as https://github.com/hakyimlab/S-PrediXcan; the correct URL is https://github.com/hakyimlab/MetaXcan. The errors have been corrected in the HTML and PDF versions of the article.
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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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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.
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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.
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Integrated Supplementary Information
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.
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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Supplementary Figures 1 and 2
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Supplementary Data Set
Top 10,000 SNPs
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Sanchez-Roige, S., Fontanillas, P., Elson, S.L. et al. Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry. Nat Neurosci 21, 16–18 (2018). https://doi.org/10.1038/s41593-017-0032-x
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DOI: https://doi.org/10.1038/s41593-017-0032-x
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