scholarly journals Genetic underpinnings of the transition from alcohol consumption to alcohol use disorder: shared and unique genetic architectures in a cross-ancestry sample

2021 ◽  
Author(s):  
Rachel L Kember ◽  
Rachel A. Vickers-Smith ◽  
Hang Zhou ◽  
Heng Xu ◽  
Cecilia Dao ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Genetic Variants ◽  
Alcohol Use Disorder ◽  
Genetic Factors ◽  
Genetic Correlations ◽  
Heavy Drinking ◽  
Direct Effects ◽  
Heavy Alcohol Consumption ◽  
Program Sample

Recent GWAS of alcohol-related traits have uncovered key differences in the underlying genetic architectures of alcohol consumption and alcohol use disorder (AUD), with the two traits having opposite genetic correlations with psychiatric disorders. Understanding the genetic factors that underlie the transition from heavy drinking to AUD has important theoretical and clinical implications. We utilized longitudinal data from the cross-ancestry Million Veteran Program sample to identify 1) novel loci associated with AUD and alcohol consumption [measured by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)] and 2) genetic variants with direct effects on AUD not mediated through alcohol consumption. We identified 26 loci associated with AUD, including 5 ancestry-specific and 6 novel loci and 22 loci associated with AUDIT-C, including 3 ancestry-specific and 8 novel loci. In secondary GWAS that excluded individuals who report abstinence, we identify 7 additional loci for AUD and 8 additional loci for AUDIT-C. We demonstrate that, although the heterogeneity of the abstinent group biases the GWAS findings, unique variance between alcohol consumption and disorder remains after the group is excluded. Finally, using mediation analysis, we identified a set of variants with effects on AUD that are not mediated through alcohol consumption. The distinct genetic architectures of alcohol consumption and AUD suggest different biological contributions to the traits. Genetic variants with direct effects on AUD are potentially relevant to understanding the transition from heavy alcohol consumption to AUD and targets for translational prevention and treatment efforts.

scholarly journals Evidence of shared genetic influences underlying schizophrenia and alcohol use disorder, but not alcohol consumption

2020 ◽  
Author(s):  
Emma C. Johnson ◽  
Manav Kapoor ◽  
Alexander S. Hatoum ◽  
Hang Zhou ◽  
Renato Polimanti ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Genetic Variants ◽  
Alcohol Use Disorder ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Genetic Covariance ◽  
Genome Wide ◽  
Brain Tissues

AbstractBackgroundAlcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and recent genome-wide association studies (GWAS) have identified significant genetic correlations between them. In parallel, mounting evidence from GWAS suggests that alcohol consumption is only weakly genetically correlated with SCZ, but this has not yet been systematically investigated.MethodsWe used the largest published GWAS for AUD (total cases = 77,822) and SCZ (total cases = 46,827) to systematically identify genetic variants that influence both disorders (in either the same or opposite direction of effect) as well as disorder-specific loci, and contrast our findings with GWAS data for drinks per week (DPW; N = 537,349) as a measure of alcohol consumption.ResultsWe identified 55 independent genome-wide significant SNPs with the same direction of effect on AUD and SCZ, 9 with robust opposite effects, and 99 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). The genetic correlation between DPW and SCZ (rg = 0.102, SE = 0.022) was significantly lower than that for AUD and SCZ (rg = 0.392, SE = 0.029; p-value of the difference = 9.3e-18), and the genetic covariance between DPW and SCZ was not enriched for any meaningful tissue-specific categories.ConclusionsOur findings provide a detailed view of genetic loci that influence risk of both AUD and SCZ, suggest that biological commonalities underlying genetic variants with an effect on both disorders are manifested in brain tissues, and provide further evidence that SCZ shares meaningful genetic overlap with AUD and not merely alcohol consumption.

Alcohol and Human Health: What Is the Evidence?

2020 ◽  
Vol 11 (1) ◽  
pp. 1-21 ◽  
Author(s):  
Henk F.J. Hendriks
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Heavy Drinking ◽  
Personal Health ◽  
Moderate Alcohol Consumption ◽  
Cancer Risk Factors ◽  
Mental Diseases ◽  
Heavy Alcohol Consumption

Alcohol consumption has long been a part of human culture. However, alcohol consumption levels and alcohol consumption patterns are associated with chronic diseases. Overall, light and moderate alcohol consumption (up to 14 g per day for women and up to 28 g per day for men) may be associated with reduced mortality risk, mainly due to reduced risks for cardiovascular disease and type-2 diabetes. However, chronic heavy alcohol consumption and alcohol abuse lead to alcohol-use disorder, which results in physical and mental diseases such as liver disease, pancreatitis, dementia, and various types of cancer. Risk factors for alcohol-use disorder are largely unknown. Alcohol-use disorder and frequent heavy drinking have detrimental effects on personal health.

scholarly journals Predictors of Symptom Course in Alcohol Use Disorder

2020 ◽  
Author(s):  
William Conlin ◽  
Kenneth J. Sher ◽  
Alvaro Vergés ◽  
Michaela Hoffman ◽  
Douglas Steinley
Keyword(s):  
Family History ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Heavy Drinking ◽  
Epidemiological Survey ◽  
Future Research ◽  
Heavy Alcohol ◽  
Heavy Alcohol Consumption ◽  
History Of

Objective: Alcohol Use Disorder (AUD) has traditionally been viewed as a chronic, progressive, relapsing disorder (Jellinek, 1960; National Institute on Drug Abuse, 2018). However, little is known about the course of individual AUD criteria. To the extent that individual symptoms represent the focus of some treatments (e.g., withdrawal, craving), understanding the course of specific symptoms, and individual differences in symptom course, can inform treatment efforts and future research directions.Method: The current study examined 34,653 participants form Wave 1 (2001-2002) and Wave 2 (2003-2004) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC; Grant, Moore, & Kaplan, 2003; Grant, Kaplan, and Stinson, 2005), using logistic regression to analyze the extent to which AUD symptom course is predicted by heavy alcohol consumption, family history of alcoholism, and lifetime diagnosis of Conduct Disorder. Results: The course of all AUD symptoms was significantly influenced by all four external criteria, with the magnitude of the prediction varying across different symptoms and different aspects of course. Conclusion: The strength of the relationship appeared to be related to the theoretical proximity of a given predictor to AUD symptomatology, with heavy drinking being the strongest and family history of AUD being the weakest. The course of all AUD symptoms was strongly associated with the prevalence of the given symptom in the overall sample. Future work should include examining the interchangeability of AUD symptoms and considering heavy alcohol consumption as a criterion for AUD diagnosis.

Nalmefene against alcohol use disorder: A report of one case

2017 ◽  
Vol 41 (S1) ◽  
pp. s866-s866
Author(s):  
M. Juncal Ruiz ◽  
O. Porta Olivares ◽  
L. Sánchez Blanco ◽  
R. Landera Rodríguez ◽  
M. Gómez Revuelta ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Opioid Receptor ◽  
Treatment Option ◽  
Withdrawal Syndrome ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Family Relationship ◽  
Heavy Drinking ◽  
Alcohol Withdrawal Syndrome

IntroductionAlcohol consumption represents a significant factor for mortality in the world: 6.3% in men and 1.1% in women. Alcohol use disorder is also very common: 5.4% in men and 1.5% in women. Despite its high frequency and the seriousness of this disorder, only 8% of all alcohol-dependents are ever treated. One potentially interesting treatment option is oriented toward reducing alcohol intake.AimsTo describe one case who has improved his alcohol consumption after starting treatment with nalmefene, an opioid receptor antagonist related to naltrexone.MethodsA 35-year-old male with alcohol use disorder since 2001 came to our consult in November 2015. He was in trouble with his family and he had a liver failure. We offer a new treatment option with nalmefene 18 mg to reduce alcohol consumption.ResultsBefore to start nalmefene he drank 21 drinks/week. Six-month later, he decreased alcohol intake until 5 drinks/week with better family relationship and liver function. After starting nalmefene he complained of nausea, so we recommend to take the middle of the pill for next 7 days. After this time he returned to take one pill with good tolerance and no more side effects or withdrawal syndrome.ConclusionsNalmefene appears to be effective and safe in reducing heavy drinking and in preventing alcohol withdrawal syndrome due to its opioid receptor antagonism. This case suggests nalmefene is a potential option to help patients, who do not want or cannot get the abstinence, in reducing their alcohol consumption.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Unhealthy Alcohol Use

2019 ◽  
Author(s):  
Stephen R Holt ◽  
Joseph H. Donroe
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Genetic Factors ◽  
Physical And Mental Health ◽  
Unhealthy Alcohol Use ◽  
Unhealthy Alcohol ◽  
Societal Norms ◽  
High Prevalence ◽  
Excessive Alcohol

Unhealthy alcohol use refers to a spectrum of alcohol consumption ranging from at-risk drinking to alcohol use disorder. It is associated with both a high cost to society and to individuals. Globally, alcohol is a leading cause of death and disability, and despite the high prevalence of unhealthy alcohol use, diagnosis, and treatment of alcohol use disorder remains disproportionately low. Risk for unhealthy alcohol use and alcohol related harms is multifactorial and includes genetic factors, gender, age, socioeconomic status, cultural and societal norms, and policies regulating alcohol consumption among others. Excessive alcohol use is associated with a myriad of poor physical and mental health outcomes, and screening for unhealthy alcohol use is universally recommended and effective. This review contains 1 figures, 2 tables, and 76 references.  Key Words: addiction, alcohol, cancer, diagnosis, drinking, liver disease, screening, stigma, use disorderImportant Advances

Unhealthy Alcohol Use

2019 ◽  
Author(s):  
Stephen R Holt ◽  
Joseph H. Donroe
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Genetic Factors ◽  
Physical And Mental Health ◽  
Unhealthy Alcohol Use ◽  
Unhealthy Alcohol ◽  
Societal Norms ◽  
High Prevalence ◽  
Excessive Alcohol

Unhealthy alcohol use refers to a spectrum of alcohol consumption ranging from at-risk drinking to alcohol use disorder. It is associated with both a high cost to society and to individuals. Globally, alcohol is a leading cause of death and disability, and despite the high prevalence of unhealthy alcohol use, diagnosis, and treatment of alcohol use disorder remains disproportionately low. Risk for unhealthy alcohol use and alcohol related harms is multifactorial and includes genetic factors, gender, age, socioeconomic status, cultural and societal norms, and policies regulating alcohol consumption among others. Excessive alcohol use is associated with a myriad of poor physical and mental health outcomes, and screening for unhealthy alcohol use is universally recommended and effective. This review contains 1 figures, 2 tables, and 76 references.  Key Words: addiction, alcohol, cancer, diagnosis, drinking, liver disease, screening, stigma, use disorderImportant Advances

Other ways for the treatment of alcohol dependence: A patient treated with nalmefene

2017 ◽  
Vol 41 (S1) ◽  
pp. S484-S484
Author(s):  
O. Porta Olivares ◽  
M. Juncal Ruiz ◽  
M. Gómez Revuelta ◽  
G. Pardo de Santayana Jenaro ◽  
L. Sánchez Blanco ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Alcohol Use Disorder ◽  
Opiate Receptors ◽  
Heavy Drinking ◽  
The European Union ◽  
Total Consumption ◽  
Excessive Alcohol Consumption ◽  
Competing Interest

IntroductionAlcohol dependence belongs to one of the major risk factors to health worldwide. Alcohol consumption is a significant factor for mortality in the world: 6.3% in men and 1.1% in women. The alcohol use disorder is also very common: 5.4% in men, 1.5% in women. Despite its high frequency and severity of this disorder, only 8% of all alcohol dependents are treated once.AimsAn interesting treatment option is geared toward reducing alcohol intake. Some patients in treatment for alcohol use disorder prefer an initial target of reducing consumption. Nalmefene, an antagonist naltrexone associated with opioid receptors, has been authorized in the European Union to help alcohol-dependent patients reduce their consumption. Antagonists’ opiate receptors are associated with reduced reward in relation to alcohol consumption, thus helping patients in reducing energy consumption.MethodsA man of 39 years old, with a diagnosis of alcohol use disorder and depressive disorder and poor outcome despite different types of treatment (as aversive agents) was treated with nalmefene.ResultsAfter a few months, nalmefene had a beneficial effect on the patient, with a significant reduction in the number of days of excessive alcohol consumption and total consumption in the sixth month. In addition, treatment was well tolerated, with no observed secondary effects.ConclusionsNalmefene appears to be effective and safe in reducing heavy drinking. Drugs such as nalmefene have demonstrated efficacy in association with a biopsychosocial approach to help patients achieve their personal objectives for this disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Multivariate GWAS elucidates the genetic architecture of alcohol consumption and misuse, corrects biases, and reveals novel associations with disease

2020 ◽  
Author(s):  
Travis T Mallard ◽  
Jeanne E Savage ◽  
Emma C Johnson ◽  
Yuye Huang ◽  
Alexis C Edwards ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Psychiatric Disorders ◽  
Alcohol Use Disorder ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Socioeconomic Outcomes ◽  
Alcohol Involvement

ABSTRACTGenome-wide association studies (GWASs) of the Alcohol Use Disorder Identification Test (AUDIT), a ten-item screener for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders/medical conditions. To explore these unexpected differences in genetic correlations, we conducted the first item-level and largest GWAS of AUDIT items (N=160,824), and applied a multivariate framework to mitigate previous biases. In doing so, we identified novel patterns of similarity (and dissimilarity) among the AUDIT items, and found evidence of a correlated two-factor structure at the genetic level (Consumption and Problems, rg=.80). Moreover, by applying empirically-derived weights to each of the AUDIT items, we constructed an aggregate measure of alcohol consumption that is strongly associated with alcohol dependence (rg=.67) and several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by performing polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, we identified novel genetic associations between alcohol consumption, alcohol misuse, and human health. Our work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD, and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.

Unhealthy Alcohol Use

2019 ◽  
Author(s):  
Stephen R Holt ◽  
Joseph H. Donroe
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Genetic Factors ◽  
Physical And Mental Health ◽  
Unhealthy Alcohol Use ◽  
Unhealthy Alcohol ◽  
Societal Norms ◽  
High Prevalence ◽  
Excessive Alcohol

Unhealthy alcohol use refers to a spectrum of alcohol consumption ranging from at-risk drinking to alcohol use disorder. It is associated with both a high cost to society and to individuals. Globally, alcohol is a leading cause of death and disability, and despite the high prevalence of unhealthy alcohol use, diagnosis, and treatment of alcohol use disorder remains disproportionately low. Risk for unhealthy alcohol use and alcohol related harms is multifactorial and includes genetic factors, gender, age, socioeconomic status, cultural and societal norms, and policies regulating alcohol consumption among others. Excessive alcohol use is associated with a myriad of poor physical and mental health outcomes, and screening for unhealthy alcohol use is universally recommended and effective. This review contains 1 figures, 2 tables, and 76 references.  Key Words: addiction, alcohol, cancer, diagnosis, drinking, liver disease, screening, stigma, use disorderImportant Advances

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