scholarly journals Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

2018 ◽  
Author(s):  
Raymond K. Walters ◽  
Mark J. Adams ◽  
Amy E. Adkins ◽  
Fazil Aliev ◽  
Silviu-Alin Bacanu ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Problem Drinking ◽  
Behavioral Outcomes ◽  
Genetic Correlations ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Dsm Iv ◽  
Family Based ◽  
The Relationship

AbstractLiability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM - IV diagnosed AD. Genome - wide data on 14,904 individuals with AD and 37,944 controls from 28 case / control and family - based studies were meta - analyzed, stratified by genetic ancestry (European, N = 46,568; African; N = 6,280). Independent, genome - wide significant effects of different ADH1B variants were identified in European (rs1229984; p = 9.8E - 13) and African ancestries (rs2066702; p = 2.2E - 9). Significant genetic correlations were observed with schizophrenia, ADHD, depression, and use of cigarettes and cannabis. There was only modest genetic correlation with alcohol consumption and inconsistent associations with problem drinking. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and non - pathological drinking behaviors.

scholarly journals Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)

2018 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
Abraham A. Palmer ◽  
Pierre Fontanillas ◽  
Sarah L. Elson ◽  
Mark J. Adams ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Dependence ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Population Based ◽  
Major Depressive ◽  
Genome Wide ◽  
Disorder Identification ◽  
Dsm Iv

AbstractAlcohol use disorders (AUD) are common conditions that have enormous social and economic consequences. We obtained quantitative measures using the Alcohol Use Disorder Identification Test (AUDIT) from two population-based cohorts of European ancestry: UK Biobank (UKB; N=121,604) and 23andMe (N=20,328) and performed a genome-wide association study (GWAS) meta-analysis. We also performed GWAS for AUDIT items 1-3, which focus on consumption (AUDIT-C), and for items 4-10, which focus on the problematic consequences of drinking (AUDIT-P). The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13; we also replicated previously identified signals in the genes ADH1B, ADH1C, KLB, and GCKR. The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (rg=0.76-0.92) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) alcohol dependence (rg=0.33-0.63). AUDIT-P and AUDIT-C showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P was positively genetically correlated with schizophrenia (rg=0.22, p=3.0×10−10), major depressive disorder (rg=0.26, p=5.6×10−3), and attention-deficit/hyperactivity disorder (ADHD; rg=0.23, p=1.1×10−5), whereas AUDIT-C was negatively genetically correlated with major depressive disorder (rg=−0.24, p=3.7×10−3) and ADHD (rg=−0.10, p=1.8×10−2). We also used the AUDIT data in the UKB to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total score of ≤4 as controls and ≥12 as cases produced a high genetic correlation with DSM-IV alcohol dependence (rg=0.82, p=3.2×10−6) while retaining most subjects. We conclude that AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and AUD.

scholarly journals Evidence of causal effect of major depression on alcohol dependence: Findings from the Psychiatric Genomics Consortium

2018 ◽  
Author(s):  
Renato Polimanti ◽  
Roseann E. Peterson ◽  
Jue-Sheng Ong ◽  
Stuart MacGregor ◽  
Alexis C. Edwards ◽  
...  
Keyword(s):  
Major Depression ◽  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Relationships ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Genetic Mechanisms ◽  
Shared Genetic

ABSTRACTBackgroundDespite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood.MethodsThis study was conducted using genome-wide data from the Psychiatric Genomics Consortium (MD: 135,458 cases and 344,901 controls; AD: 10,206 cases and 28,480 controls) and UK Biobank (AC-Frequency: from “daily or almost daily” to “never”, 438,308 individuals; AC-Quantity: total units of alcohol per week, 307,098 individuals). Linkage disequilibrium score regression and Mendelian Randomization (MR) analyses were applied to investigate shared genetic mechanisms (horizontal pleiotropy) and causal relationships (mediated pleiotropy) among these traits.OutcomesPositive genetic correlation was observed between MD and AD (rgMD-AD=+0.47, P=6.6×10-10). AC-Quantity showed positive genetic correlation with both AD (rgAD-AC-Quantity=+0.75, P=1.8×10-14) and MD (rgMD-AC-Quantity=+0.14, P=2.9×10-7), while there was negative correlation of AC-Frequency with MD (rgMD-AC-Frequency=-0.17, P=1.5×10-10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e., causal relationship) with a causal role of MD on AD (beta=0.28, P=1.29×10-6) that does not appear to be biased by confounding such as horizontal pleiotropy. No evidence of reverse causation was observed as the AD genetic instrument did not show a causal effect on MD.InterpretationResults support a causal role for MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity not only addresses important public health concerns but also has the potential to facilitate prevention and intervention efforts.FundingNational Institute of Mental Health and National Institute on Drug Abuse.Putting data into contextEvidence before this studyWe searched PubMed up to August 24, 2018, for research studies that investigated causality among alcohol-and depression related phenotypes using Mendelian randomization approaches. We used the search terms “alcohol” AND “depression” AND “Mendelian Randomization”. No restrictions were applied to language, date, or article type. Ten articles were retrieved, but only two were focused on alcohol consumption and depression-related traits. The studies were based on genetic variants in alcohol dehydrogenase (ADH) genes only, did not find evidence for a causal effect of alcohol consumption on depression phenotypes, with one study finding a causal effect of alcohol consumption on alcoholism. Both studies noted that future studies are needed with increased sample sizes and clinically derived phenotypes. To our knowledge, no previous study has applied two-sample Mendelian randomization to investigate causal relationships between alcohol dependence and major depression.Twin studies show genetic factors influence susceptibility to MD, AD, and alcohol consumption. Differently from observational approaches where several studies have investigated the relationship between alcohol-and depression-related phenotypes, very limited use of molecular genetic data has been applied to investigate this issue. Additionally, the use of genetic information has been shown to be less biased by confounders and reverse causation than observation data. However, genetic approaches, like Mendelian randomization, require large sample sizes to be informative.Added value of this studyIn this study, we used genome-wide data from the Psychiatric Genomic Consortium and UK Biobank, which include information regarding hundred thousands of individuals, to test the presence of shared genetic mechanisms and causal relationships among major depression, alcohol dependence, and alcohol consumption. The results support a causal influence of MD on AD, while alcohol consumption showed shared genetic mechanisms with respect to both major depression and alcohol dependence.Implications of all the available evidenceGiven the significant morbidity and mortality associated with MD, AD, and the comorbid condition, understanding mechanisms underlying these associations not only address important public health concerns but also has the potential to facilitate prevention and intervention efforts.

Symptoms of Alcohol Dependence Predict Suicide Ideation Among Alaskan Undergraduates

Crisis ◽  
2016 ◽  
Vol 37 (3) ◽  
pp. 232-235 ◽  
Author(s):  
Christopher R. DeCou ◽  
Monica C. Skewes
Keyword(s):  
Depressive Symptoms ◽  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Suicide Ideation ◽  
Alcohol Problems ◽  
Future Research ◽  
Causal Mechanism ◽  
Students At Risk ◽  
The Relationship ◽  
Alcohol Related Problems

Abstract. Background: Previous research has demonstrated an association between alcohol-related problems and suicidal ideation (SI). Aims: The present study evaluated, simultaneously, alcohol consequences and symptoms of alcohol dependence as predictors of SI after adjusting for depressive symptoms and alcohol consumption. Method: A sample of 298 Alaskan undergraduates completed survey measures, including the Young Adult Alcohol Consequences Questionnaire, the Short Alcohol Dependence Data Questionnaire, and the Beck Depression Inventory – II. The association between alcohol problems and SI status was evaluated using sequential logistic regression. Results: Symptoms of alcohol dependence (OR = 1.88, p < .05), but not alcohol-related consequences (OR = 1.01, p = .95), emerged as an independent predictor of SI status above and beyond depressive symptoms (OR = 2.39, p < .001) and alcohol consumption (OR = 1.08, p = .39). Conclusion: Alcohol dependence symptoms represented a unique risk for SI relative to alcohol-related consequences and alcohol consumption. Future research should examine the causal mechanism behind the relationship between alcohol dependence and suicidality among university students. Assessing the presence of dependence symptoms may improve the accuracy of identifying students at risk of SI.

scholarly journals From Cannabis to Problem Drinking? Use and Abuse from Youth to Adulthood

2014 ◽  
Vol 0 (0) ◽  
Author(s):  
Christer Hyggen ◽  
Torild Hammer
Keyword(s):  
Alcohol Consumption ◽  
Problem Drinking ◽  
Total N ◽  
Level Of Involvement ◽  
Roles And Responsibilities ◽  
Nationally Representative ◽  
Adult Roles ◽  
The Life Course ◽  
The Relationship ◽  
Alcohol Related Problems

AbstractAIMS – The transition from youth to adulthood is associated with changes in the consumption of drugs and alcohol. The aim is to explore the process of “maturing out” of high levels of alcohol consumption, substance use and alcohol related problems from youth to adulthood. We are particularly interested in the relationship between the use of cannabis and alcohol consumption in relation to indicators of adult roles and responsibilities and alcohol-related problems over the life-course. METHODS – We used data from the longitudinal panel survey Arbeid, Livsstil og Helse (ALH). The data contains information on alcohol and drug consumption, alcohol related problems and a range of indicators of adulthood like marriage and parenthood from surveys repeated in 1985, 1987, 1989, 1993, 2003 and 2010. The sample was nationally representative for the cohorts born 1965–1968 and thus contains individual histories from youth (17–20 years) to adulthood (42–45 years) with response rates ranging from 80% in 1985 to 53% in 2010 (total n=1997). RESULTS – Alcohol consumption is found to be substantially higher among users of cannabis than among non-users throughout the period from youth to adulthood. The use of cannabis, the level of alcohol consumption and probability of experiencing alcohol related problems decrease as the cohorts grow older. Alcohol related problems are still associated with the level of involvement with cannabis: those with a current or previous involvement with cannabis report more alcohol related problems. Taking into account the decreasing trend of alcohol related problems with age we find that becoming a parent and/ or getting married reduces the risk of experiencing such problems.

scholarly journals Potential influence of socioeconomic status on genetic correlations between alcohol consumption measures and mental health

2019 ◽  
Vol 50 (3) ◽  
pp. 484-498 ◽  
Author(s):  
Andries T. Marees ◽  
Dirk J. A. Smit ◽  
Jue-Sheng Ong ◽  
Stuart MacGregor ◽  
Jiyuan An ◽  
...  
Keyword(s):  
Mental Health ◽  
Substance Use ◽  
Alcohol Consumption ◽  
Genetic Correlations ◽  
High Alcohol ◽  
Genetic Associations ◽  
Potential Influence ◽  
High Alcohol Consumption ◽  
Genome Wide ◽  
Consumption Frequency

AbstractBackground. Frequency and quantity of alcohol consumption are metrics commonly used to measure alcohol consumption behaviors. Epidemiological studies indicate that these alcohol consumption measures are differentially associated with (mental) health outcomes and socioeconomic status (SES). The current study aims to elucidate to what extent genetic risk factors are shared between frequency and quantity of alcohol consumption, and how these alcohol consumption measures are genetically associated with four broad phenotypic categories: (i) SES; (ii) substance use disorders; (iii) other psychiatric disorders; and (iv) psychological/personality traits.Methods. Genome-Wide Association analyses were conducted to test genetic associations with alcohol consumption frequency (N = 438 308) and alcohol consumption quantity (N = 307 098 regular alcohol drinkers) within UK Biobank. For the other phenotypes, we used genome-wide association studies summary statistics. Genetic correlations (rg) between the alcohol measures and other phenotypes were estimated using LD score regression.Results. We found a substantial genetic correlation between the frequency and quantity of alcohol consumption (rg = 0.52). Nevertheless, both measures consistently showed opposite genetic correlations with SES traits, and many substance use, psychiatric, and psychological/personality traits. High alcohol consumption frequency was genetically associated with high SES and low risk of substance use disorders and other psychiatric disorders, whereas the opposite applies for high alcohol consumption quantity.Conclusions. Although the frequency and quantity of alcohol consumption show substantial genetic overlap, they consistently show opposite patterns of genetic associations with SES-related phenotypes. Future studies should carefully consider the potential influence of SES on the shared genetic etiology between alcohol and adverse (mental) health outcomes.

Patterns of alcohol consumption and psychiatric disorders among Ontario adults

1997 ◽  
Vol 24 (3) ◽  
pp. 533-556 ◽  
Author(s):  
Helen Ross ◽  
Jürgen Rehm ◽  
Gordon Walsh
Keyword(s):  
Mental Health ◽  
Alcohol Consumption ◽  
Psychiatric Disorders ◽  
Problem Drinking ◽  
Composite International Diagnostic Interview ◽  
Diagnostic Interview ◽  
University Of Michigan ◽  
And Gender ◽  
The University ◽  
The Relationship

This study examined the relationship between patterns of alcohol consumption, including problem drinking, and psychiatric disorders in the general population. The paper utilizes data on 8,116 adults age 15–64 living in households who were interviewed for the Ontario Health Survey and the Mental Health Supplement. The University of Michigan Composite International Diagnostic Interview (UM-CIDI) was administered by trained lay interviewers to generate lifetime DSM-III-R diagnoses. Unlike previous studies, the results of this study provided no evidence of a U-shaped or J-shaped curve or relationship between alcohol use and mental health. Lifetime abstainers had the lowest risks for all mental disorders examined, while former at-risk drinkers (those who had not had a drink in the previous year but at one time regularly drank more than 12 drinks a week) had the highest risks, even after adjustment for age and gender.

scholarly journals Is Alcohol Consumption Associated with Poor Perceived Academic Performance? Survey of Undergraduates in Finland

2020 ◽  
Vol 17 (4) ◽  
pp. 1369 ◽  
Author(s):  
Walid El Ansari ◽  
Abdul Salam ◽  
Sakari Suominen
Keyword(s):  
Logistic Regression ◽  
Academic Performance ◽  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Parental Education ◽  
Problem Drinking ◽  
Heavy Episodic Drinking ◽  
Sociodemographic Characteristics ◽  
Living Situation ◽  
Alcohol Behaviors

The relationship between academic performance and alcohol consumption among students remains inconsistent. We assessed this relationship, controlling for sociodemographic characteristics across seven faculties at the University of Turku (1177 undergraduates). An online questionnaire assessed: seven sociodemographic characteristics (age, gender, year/discipline of study, accommodation type, being in intimate relationship, parental education, and income sufficiency); two perceived academic performance (students’ subjective importance of achieving good grades and students’ appraisal of their academic performance compared to peers); and six alcohol consumption behaviors (length of time, amount consumed, frequency, heavy episodic drinking, problem drinking, and possible alcohol dependence). Simple logistic regression assessed relationships between sociodemographic and academic variables with alcohol consumption behaviors; multiple logistic regression assessed the same relationships after controlling for all other variables. Students reported long duration and large amount of drinking (46% and 50%), high frequency of drinking (41%), heavy episodic drinking (66%), problem drinking (29%), and possible alcohol dependence (9%). After controlling, gender was associated with all alcohol consumption behaviors, followed by religiosity (associated with four alcohol behaviors), living situation, marital status, age (each associated with two alcohol behaviors), and parental education and year of study (each associated with one alcohol behavior). Study discipline, income sufficiency, importance of achieving good grades, and academic performance compared to peers were not associated with any alcohol behaviors. Universities need to assess problem drinking and alcohol use disorders among students. Prevention strategies are required to reduce risk. Health promotion efforts could focus on beliefs and expectations about alcohol and target student groups at risk for more efficient and successful efforts.

Abstract 04: Using family-based genome-wide data to evaluate imprinting and maternal genetic effects: A pilot study of glioma risk.

2012 ◽  
Vol 21 (11 Supplement) ◽  
pp. 04-04
Author(s):  
Philip J. Lupo ◽  
Michael E. Scheurer ◽  
Georgina N. Armstrong ◽  
Spiridon Tsavachidis ◽  
Yanhong Liu ◽  
...  
Keyword(s):  
Pilot Study ◽  
Genetic Effects ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Glioma Risk ◽  
Family Based

scholarly journals Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

2019 ◽  
Vol 49 (07) ◽  
pp. 1218-1226 ◽  
Author(s):  
Renato Polimanti ◽  
Roseann E. Peterson ◽  
Jue-Sheng Ong ◽  
Stuart MacGregor ◽  
Alexis C. Edwards ◽  
...  
Keyword(s):  
Major Depression ◽  
Alcohol Dependence ◽  
Genetic Correlation ◽  
Causal Relationship ◽  
Causal Effect ◽  
Uk Biobank ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Genetic Mechanisms ◽  
Shared Genetic

AbstractBackgroundDespite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.MethodsLinkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).ResultsPositive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.ConclusionThis study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.

Reasons why Young Adults do or do not Seek help for Alcohol Problems

2007 ◽  
Vol 41 (12) ◽  
pp. 1005-1012 ◽  
Author(s):  
J. Elisabeth Wells ◽  
L. John Horwood ◽  
David M. Fergusson
Keyword(s):  
Young Adults ◽  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Practical Reason ◽  
Specific Treatment ◽  
Alcohol Problems ◽  
Seeking Help ◽  
Dsm Iv ◽  
Almost All ◽  
Drinking Occasion

Objective:To investigate reasons for seeking or not seeking help for alcohol problems in young adults and to report outcomes in those with problems who thought they did not need help. Methods:A total of 1003 members of a birth cohort were interviewed at age 25 about the period since the previous interview at age 21. DSM-IV diagnoses were made from reports of alcohol problems over the previous 4 years. Treatment contact for drinking or problems associated with drinking and reasons for seeking or not seeking help were reported. Alcohol consumption was reported for the year before interview. Results:Alcohol-specific treatment contact was uncommon: 26 of 351 with any alcohol problems made contact (7%). Even in the subgroup with alcohol dependence, only 24% made contact (13/55). Most (19/26) sought treatment because they felt they needed it. Of those with problems who did not seek help or advice, nearly all (96%) thought they did not need help. Approximately one-quarter thought the problem would get better by itself (29%) or did not think to seek help (25%). No more than 5% reported any other attitudinal or practical reason. Outcomes in the year before interview for those who thought they did not need help showed that 75% continued to experience problems and almost all drank well above guidelines at least on their heaviest drinking occasion. Only 43% had attempted to quit or cut down on their drinking. Conclusions:Alcohol-related problems were experienced by approximately one-third of these young adults but treatment contact for these problems was uncommon. Belief in ability to handle problems oneself was often not matched by action.

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