The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates.
| Title: | The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates. |
|---|---|
| Authors: | Hatoum AS; Washington University School of Medicine, Department of Psychiatry, Saint Louis, MO, USA. ashatoum@wustl.edu.; Johnson EC; Washington University School of Medicine, Department of Psychiatry, Saint Louis, MO, USA.; Colbert SMC; Washington University School of Medicine, Department of Psychiatry, Saint Louis, MO, USA.; Polimanti R; Department of Psychiatry, Division of Human Genetics, Yale School of Medicine, New Haven, CT, USA.; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.; Zhou H; Department of Psychiatry, Division of Human Genetics, Yale School of Medicine, New Haven, CT, USA.; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.; Walters RK; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Gelernter J; Department of Psychiatry, Division of Human Genetics, Yale School of Medicine, New Haven, CT, USA.; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.; Department of Genetics, Yale School of Medicine, New Haven, CT, USA.; Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.; Edenberg HJ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.; Bogdan R; Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA.; Agrawal A; Washington University School of Medicine, Department of Psychiatry, Saint Louis, MO, USA. |
| Source: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2022 Sep; Vol. 47 (10), pp. 1739-1745. Date of Electronic Publication: 2021 Nov 08. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8904907 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1740-634X (Electronic) Linking ISSN: 0893133X NLM ISO Abbreviation: Neuropsychopharmacology Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2003- : London : Nature Publishing Group; Original Publication: [New York, NY] : Elsevier, [c1987- |
| MeSH Terms: | Substance-Related Disorders*/epidemiology ; Substance-Related Disorders*/genetics ; Behavior, Addictive* ; Opioid-Related Disorders*; Alcohol Drinking/genetics ; Genome-Wide Association Study ; Humans ; Risk Factors |
| Abstract: | Substance use disorders commonly co-occur with one another and with other psychiatric disorders. They share common features including high impulsivity, negative affect, and lower executive function. We tested whether a common genetic factor undergirds liability to problematic alcohol use (PAU), problematic tobacco use (PTU), cannabis use disorder (CUD), and opioid use disorder (OUD) by applying genomic structural equation modeling to genome-wide association study summary statistics for individuals of European ancestry (Total N = 1,019,521; substance-specific Ns range: 82,707-435,563) while adjusting for the genetics of substance use (Ns = 184,765-632,802). We also tested whether shared liability across SUDs is associated with behavioral constructs (risk-taking, executive function, neuroticism; Ns = 328,339-427,037) and non-substance use psychopathology (psychotic, compulsive, and early neurodevelopmental disorders). Shared genetic liability to PAU, PTU, CUD, and OUD was characterized by a unidimensional addiction risk factor (termed The Addiction-Risk-Factor, independent of substance use. OUD and CUD demonstrated the largest loadings, while problematic tobacco use showed the lowest loading. The Addiction-Risk-Factor was associated with risk-taking, neuroticism, executive function, and non-substance psychopathology, but retained specific variance before and after accounting for the genetics of substance use. Thus, a common genetic factor partly explains susceptibility for alcohol, tobacco, cannabis, and opioid use disorder. The Addiction-Risk-Factor has a unique genetic architecture that is not shared with normative substance use or non-substance psychopathology, suggesting that addiction is not the linear combination of substance use and psychopathology.; (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.) |
| Comments: | Comment in: Neuropsychopharmacology. 2022 Sep;47(10):1735-1736. doi: 10.1038/s41386-021-01245-6.. (PMID: 34873297) |
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| Grant Information: | K02 DA032573 United States DA NIDA NIH HHS; R21 AA027827 United States AA NIAAA NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS; R01 DA054869 United States DA NIDA NIH HHS; R21 DA047527 United States DA NIDA NIH HHS; I01 BX006482 United States BX BLRD VA; I01 CX001849 United States CX CSRD VA; T32 DA007261 United States DA NIDA NIH HHS; U01 MH109532 United States MH NIMH NIH HHS; F32 AA027435 United States AA NIAAA NIH HHS |
| Entry Date(s): | Date Created: 20211109 Date Completed: 20220815 Latest Revision: 20250728 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9372072 |
| DOI: | 10.1038/s41386-021-01209-w |
| PMID: | 34750568 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.