Alcohol and cigarette smoking consumption as genetic proxies for alcohol misuse and nicotine dependence

Sanchez‐Roige, Sandra; Cox, Nancy J.; Johnson, Eric O.; Hancock, Dana B.; Davis, Lea K.

doi:10.1016/j.drugalcdep.2021.108612

Cited by 15 publications

(13 citation statements)

References 17 publications

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“…Third, we examine whether The Addiction-Risk-Factor is associated with the 3 factors representing genetic liability to non-substance psychopathology 14 (i.e., psychotic, compulsive, and neurodevelopment) and whether stage-based addiction constructs (i.e., risk-taking, executive function, neuroticism) indirectly link The Addiction-Risk-Factor to psychopathology. Finally, given that genetic liability to substance use (e.g., ever using, quantity-frequency) and later stages of SUDs are partially distinct 7,12,13 , we repeat all analyses while incorporating genetic liability to substance use (i.e., alcohol drinks/week 26 ; tobacco ever regularly use 26 , cannabis ever use 27 ) as covariates.…”

Section: The Current Studymentioning

confidence: 99%

The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates

Hatoum

Johnson

Colbert

et al. 2021

Neuropsychopharmacol.

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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 modelling to genomewide 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 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.The MVP summary statistics were obtained via an approved dbGaP application (phs001672.v4.p1). The authors thank Million Veteran Program (MVP) staff, researchers, and volunteers, who have contributed to MVP, and especially participants who previously served their country in the military and now generously agreed to enroll in the study. (For details, see https://www.research.va.gov/mvp/ and Gaziano, J.M. et al. Million Veteran Program: A megabiobank to study genetic influences on health and disease. J Clin Epidemiol 70, 214-23 (2016)). This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by the Veterans Administration (VA) Cooperative Studies Program (CSP) award #G002. This study included summary statistics of a genetic study on cannabis use (Pasman et al, 2018 Nature Neuroscience). We would like to acknowledge all participating groups of the International Cannabis Consortium, and in particular the members of the working group including Joelle Pasman, Karin Verweij, Nathan Gillespie, Eske Derks, and Jacqueline Vink. Pasman et al, (2018) included data from the UK Biobank resource under application numbers 9905, 16406 and 25331.

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Section: The Current Studymentioning

confidence: 99%

The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates

Hatoum

Johnson

Colbert

et al. 2021

Neuropsychopharmacol.

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“…84,85,87,108,109 However, these associations also extend to other substances (tobacco, alcohol, general SUD). 85,89,110 A plausible mechanism underlying these associations may be explained by reward mechanisms that substances (particularly, opioids) act upon. To date, there are no studies using causal methods to explore these comorbidities and common pathways.…”

Section: Chronic Painmentioning

confidence: 99%

Substance use and common contributors to morbidity: A genetics perspective

Sanchez‐Roige¹,

Kember²,

Agrawal³

2022

eBioMedicine

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“…We used summary statistics from the GWAS of the Fagerström Test for Nicotine Dependence 25 (FTND). As cigarettes per day is an item within the FTND and the genetic correlation between FTND and cigarettes per day is high (calculated rG = 0.97 CI = .12) 12 , we combined CPD And FTND into a single indicator. We applied Multi-Trait Analysis of Genome-wide association study summary statistics (MTAG 31 ) to summary statistics generated from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) GWAS of cigarettes per day to create the combined problematic tobacco use (PTU) phenotype 26 .…”

Section: Problematic Tobacco Use (Ptu)mentioning

confidence: 99%

The Addiction Risk Factor: A Unitary Genetic Vulnerability Characterizes Substance Use Disorders and Their Associations with Common Correlates

Hatoum

Johnson²,

Polimanti

et al. 2021

Preprint

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BackgroundSubstance use disorders (SUDs) 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 estimate the shared genetic architecture across distinct SUDs, its independence from genetic liability to substance use, and its relation to genetic liability to impulsivity, negative affect, and executive function as well as non-substance psychopathology.MethodsWe 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 modelling to genome-wide association study statistics (Total N = 1,019,521; substance specific Ns range: 82,707-435,563 of European ancestry), while adjusting for the genetics of substance use (Ns = 184,765-632,802). We 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 (mood/psychotic, compulsive, and early neurodevelopmental disorders).ResultsShared genetic liability to PAU, PTU, CUD, and OUD was characterized by a unidimensional addiction factor (termed a(g)), independent of substance use. OUD and CUD demonstrated the largest loadings. a(g) was associated with risk taking, neuroticism, executive function, and non-substance psychopathology, but retained specific variance (standardized residual= .579).InterpretationA common genetic addictions factor partly explains susceptibility for alcohol, tobacco, cannabis and opioid use disorder. a(g) has unique pathways that are not shared with substance use or non-substance psychopathology, suggesting that addiction is not the linear combination of substance use and psychopathology.

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Alcohol and cigarette smoking consumption as genetic proxies for alcohol misuse and nicotine dependence

Cited by 15 publications

References 17 publications

The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates

The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates

Substance use and common contributors to morbidity: A genetics perspective

The Addiction Risk Factor: A Unitary Genetic Vulnerability Characterizes Substance Use Disorders and Their Associations with Common Correlates

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