Dataset Information

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.

ABSTRACT: Background:Observational studies have shown that tobacco and alcohol use co-occur, but it is not clear whether this relationship is causal. Methods:Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank, we used observational methods to test the hypothesis that smoking heaviness increases alcohol consumption. Mendelian randomization (MR) analyses were then used to test the causal relationship between smoking heaviness and alcohol consumption using 55 967 smokers from four European studies [ALSPAC, The Nord-Trøndelag Health Study (HUNT), the Copenhagen General Population Study (CGPS) and UK Biobank]. MR analyses used rs1051730/rs16969968 as a genetic proxy for smoking heaviness. Results:Observational results provided evidence of an association between cigarettes per day and weekly alcohol consumption (increase in units of alcohol per additional cigarette smoked per day = 0.10, 95% confidence interval (CI) 0.05 to 0.15, P ? 0.001 in ALSPAC; and 0.48, 95% CI 0.45 to 0.52, P ? 0.001 in UK Biobank). However, there was little evidence for an association between rs1051730/rs16969968 and units of alcohol consumed per week across ALSPAC, HUNT, CGPS and UK Biobank (standard deviation increase in units of alcohol per additional copy of the risk allele = -0.004, 95% CI -0.023 to 0.016, P=0.708, I2 = 51.9%). We had 99% and 88% power to detect a change of 0.03 and 0.02 standard deviation units of alcohol per additional copy of the risk allele, respectively. Conclusions:Previously reported associations between smoking and alcohol are unlikely to be causal, and may be the result of confounding and/or reverse causation. This has implications for public health research and intervention research.

SUBMITTER: Taylor M

PROVIDER: S-EPMC6124618 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.

Taylor Michelle M Rode Line L Bjørngaard Johan J Taylor Amy E AE Bojesen Stig E SE Åsvold Bjørn O BO Gabrielsen Maiken E ME Lewis Glyn G Nordestgaard Børge G BG Romundstad Pål R PR Hickman Matthew M Munafò Marcus R MR

International journal of epidemiology 20180801 4

<h4>Background</h4>Observational studies have shown that tobacco and alcohol use co-occur, but it is not clear whether this relationship is causal.<h4>Methods</h4>Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank, we used observational methods to test the hypothesis that smoking heaviness increases alcohol consumption. Mendelian randomization (MR) analyses were then used to test the causal relationship between smoking heaviness and alcohol consumption us ...[more]

PMID: 29509885

Similar Datasets

Project description:BackgroundThe correlation between smoking and alcohol consumption and the development of Dupuytren's disease (DD) has been acknowledged. However, the definitive causal relationship between these two factors and DD remains elusive. In order to establish a causal connection, we employed the two-sample Mendelian randomization method to evaluate the relationship between smoking and alcohol consumption and DD.MethodsBased on publicly available genome-wide association studies (GWAS), two-sample univariate MR analyses were performed to assess the causal effects of drinks per week, cigarettes per day, smoking initiation, age of initiation, and smoking cessation on DD. We used inverse variance weighted (IVW) to generate the primary results for the MR analysis. Furthermore, we performed sensitivity MR analyses based on various methods to assess the robustness of estimations. Bidirectional MR analyses were used to study the interaction between smoking and alcohol consumption. Multivariate MR analyses were used to obtain independent causal effects of smoking or drinking on DD.ResultsOur two-sample MR, which was predominately based on IVW, revealed a causal relationship between drinks per week and DD (OR = 2.948, 95%CI: 1.746-4.975, P = 5.16E-05). In addition, there is no causal association between cigarettes per day, smoking initiation, age of initiation, smoking cessation and DD. Similar conclusions were reached by other MR methods. The results of the bidirectional MR analyses showed that the causal relationships between age of initiation and drinks per week were robust and significant. Multivariate MR results indicated that the causal effect of alcohol consumption on DD was independent of smoking.ConclusionOur Mendelian Randomization study indicated that there is a causality between drinking alcohol and DD, but no such causality was found between smoking and DD. This is the first study to prove that drinking alcohol could cause DD. This could help people who are trying to prevent DD from happening in the first place.

Project description:BackgroundClozapine is an effective antipsychotic medication for patients with treatment-resistant schizophrenia. Previous studies revealed that smoking, alcohol intake, and coffee consumption altered the metabolism of clozapine. However, causal associations between substance use and clozapine levels were not sufficiently established.MethodsSeveral genome-wide association studies provided genetic tools for six measures of substance use, including age of smoking, cigarettes per day, smoking cessation, smoking initiation, coffee consumption, and alcohol consumption (GWASs). Utilizing the CLOZUK consortium's dataset, their associations with clozapine and its metabolite concentrations were evaluated. All GWAS data were collected from the European population. Mendelian randomization (MR) estimations from each genetic test were combined using inverse variance weighted (IVW) meta-analysis in combination with complementing techniques (such as weighted median and MR Egger). We also analyze horizontal pleiotropy and heterogeneity using various sensitivity analyses.ResultsGenetically predicted higher level of smoking initiation was significantly associated with reduced clozapine (β = -0.14, P = 4.53E-04) concentrations and norclozapine concentrations (β = -0.14, P = 3.33E-04), and increased coffee consumption was significantly associated with lower level of clozapine concentrations (β = -0.42, P = 1.70E-14), norclozapine concentrations (β = -0.27, P = 1.51E-07), and the metabolic ratio of clozapine to norclozapine (β = -0.15, P = 5.35E-07), survived after the Bonferroni correction (P = 0.05/6 = 0.008). In sensitivity analyses, the weighted median and MR Egger methods demonstrated directionally consistent effects. In addition, our sensitive test indicated no significant horizontal pleiotropy and heterogeneity (P > 0.05). However, other measures of substance use (age of initiation smoking, cigarettes per day, smoking cessation, and drinks per week) were not associated with clozapine metabolism.ConclusionOur investigation revealed a correlation between greater smoking initiation and coffee consumption and reduced blood levels of clozapine and norclozapine. Providing clinicians with guidance on how to adjust clozapine levels for clozapine-treated patients.

Project description:BackgroundAlterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure.MethodsGenome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy.FindingsAt the global level, albuminuria decreased TH (β = -0.07 mm, 95% CI: -0.12 mm to -0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (β = -0.11 mm, 95% CI: -0.16 mm to -0.07 mm, P = 3.74×10-6). No pleiotropy was detected.InterpretationKidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis.FundingThis study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).

Project description:Background and aimsInitial use of drugs such as tobacco and alcohol may lead to subsequent more problematic drug use-the 'gateway' hypothesis. However, observed associations may be due to a shared underlying risk factor, such as trait impulsivity. We used bidirectional Mendelian randomization (MR) to test the gateway hypothesis.DesignOur main method was inverse-variance weighted (IVW) MR, with other methods included as sensitivity analyses (where consistent results across methods would raise confidence in our primary results). MR is a genetic instrumental variable approach used to support stronger causal inference in observational studies.Setting and participantsGenome-wide association summary data among European ancestry individuals for smoking initiation, alcoholic drinks per week, cannabis use and dependence, cocaine and opioid dependence (n = 1749-1 232 091).MeasurementsGenetic variants for exposure.FindingsWe found evidence of causal effects from smoking initiation to increased drinks per week [(IVW): β = 0.06; 95% confidence interval (CI) = 0.03-0.09; P = 9.44 × 10-06 ], cannabis use [IVW: odds ratio (OR) = 1.34; 95% CI = 1.24-1.44; P = 1.95 × 10-14 ] and cannabis dependence (IVW: OR = 1.68; 95% CI = 1.12-2.51; P = 0.01). We also found evidence of an effect of cannabis use on the increased likelihood of smoking initiation (IVW: OR = 1.39; 95% CI = 1.08-1.80; P = 0.01). We did not find evidence of an effect of drinks per week on other substance use outcomes, except weak evidence of an effect on cannabis use (IVW: OR = 0.55; 95% CI = 0.16-1.93; P-value = 0.35). We found weak evidence of an effect of opioid dependence on increased drinks per week (IVW: β = 0.002; 95% CI = 0.0005-0.003; P = 8.61 × 10-03 ).ConclusionsBidirectional Mendelian randomization testing of the gateway hypothesis reveals that smoking initiation may lead to increased alcohol consumption, cannabis use and cannabis dependence. Cannabis use may also lead to smoking initiation and opioid dependence to alcohol consumption. However, given that tobacco and alcohol use typically begin before other drug use, these results may reflect a shared risk factor or a bidirectional effect for cannabis use and opioid dependence.

Dataset Information

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.

Publications

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets