Genetic influences on delayed reward discounting: A genome-wide prioritized subset approach

James MacKillop; Joshua C. Gray; Jessica Weafer; Sandra Sanchez-Roige; Abraham A. Palmer; Harriet De Wit

doi:10.1037/pha0000227

Genetic influences on delayed reward discounting: A genome-wide prioritized subset approach

James MacKillop, Joshua C. Gray, Jessica Weafer, Sandra Sanchez-Roige, Abraham A. Palmer, Harriet De Wit

Psychology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Delayed reward discounting (DRD) is a behavioral economic measure of impulsivity that has been consistently associated with addiction. It has also been identified as a promising addiction endophenotype, linking specific sources of genetic variation to individual risk. A challenge in the studies to date is that levels of DRD are often confounded with prior drug use, and previous studies have also had limited genomic scope. The current investigation sought to address these issues by studying DRD in healthy young adults with low levels of substance use (N = 986; 62% female, 100% European ancestry) and investigating genetic variation genome-wide. The genome-wide approach used a prioritized subset design, organizing the tests into theoretically and empirically informed categories and apportioning power accordingly. Three subsets were used: (a) a priori loci implicated by previous studies; (b) high-value addiction (HVA) markers from the recently developed SmokeScreen array; and (c) an atheoretical genome-wide scan. Among a priori loci, a nominally significant association was present between DRD and rs521674 in ADRA2A. No significant HVA loci were detected. One statistically significant genome-wide association was detected (rs13395777, p = 2.8 X 10∼8), albeit in an intergenic region of unknown function. These findings are generally not supportive of the previous candidate gene studies and suggest that DRD has a complex genetic architecture that will require considerably larger samples to identify genetic associations more definitively.

Original language	English
Pages (from-to)	29-37
Number of pages	9
Journal	Experimental and Clinical Psychopharmacology
Volume	27
Issue number	1
DOIs	https://doi.org/10.1037/pha0000227
State	Published - Feb 2019

Bibliographical note

Funding Information:
All authors made substantive contributions to the research reported, and all authors have read and approved the final manuscript. The authors acknowledge the outstanding contributions of the research staff in executing the reported research including the bioinformatics support of Kyle Hernandez at the University of Chicago and are grateful for access to the SmokeScreen loci from James Baurley. This article was supported in part by National Institutes of Health Grant R01DA032015 and by the Peter Boris Chair in Addictions Research. The funding source had no other role other than financial support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No authors have potential conflicts of interest to declare, with the exception of James MacKillop who discloses that he is a principal in BEAM Diagnostics, Inc.

Publisher Copyright:
© 2018 American Psychological Association.

Keywords

Decision making
Delayed reward discounting
Genetics
Genomics
Impulsivity

ASJC Scopus subject areas

Pharmacology
Psychiatry and Mental health
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1037/pha0000227

Cite this

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abstract = "Delayed reward discounting (DRD) is a behavioral economic measure of impulsivity that has been consistently associated with addiction. It has also been identified as a promising addiction endophenotype, linking specific sources of genetic variation to individual risk. A challenge in the studies to date is that levels of DRD are often confounded with prior drug use, and previous studies have also had limited genomic scope. The current investigation sought to address these issues by studying DRD in healthy young adults with low levels of substance use (N = 986; 62% female, 100% European ancestry) and investigating genetic variation genome-wide. The genome-wide approach used a prioritized subset design, organizing the tests into theoretically and empirically informed categories and apportioning power accordingly. Three subsets were used: (a) a priori loci implicated by previous studies; (b) high-value addiction (HVA) markers from the recently developed SmokeScreen array; and (c) an atheoretical genome-wide scan. Among a priori loci, a nominally significant association was present between DRD and rs521674 in ADRA2A. No significant HVA loci were detected. One statistically significant genome-wide association was detected (rs13395777, p = 2.8 X 10∼8), albeit in an intergenic region of unknown function. These findings are generally not supportive of the previous candidate gene studies and suggest that DRD has a complex genetic architecture that will require considerably larger samples to identify genetic associations more definitively.",

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author = "James MacKillop and Gray, {Joshua C.} and Jessica Weafer and Sandra Sanchez-Roige and Palmer, {Abraham A.} and {De Wit}, Harriet",

note = "Funding Information: All authors made substantive contributions to the research reported, and all authors have read and approved the final manuscript. The authors acknowledge the outstanding contributions of the research staff in executing the reported research including the bioinformatics support of Kyle Hernandez at the University of Chicago and are grateful for access to the SmokeScreen loci from James Baurley. This article was supported in part by National Institutes of Health Grant R01DA032015 and by the Peter Boris Chair in Addictions Research. The funding source had no other role other than financial support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No authors have potential conflicts of interest to declare, with the exception of James MacKillop who discloses that he is a principal in BEAM Diagnostics, Inc. Publisher Copyright: {\textcopyright} 2018 American Psychological Association.",

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doi = "10.1037/pha0000227",

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AU - De Wit, Harriet

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Genetic influences on delayed reward discounting: A genome-wide prioritized subset approach

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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