Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
32276208
TITLE
Investigating the genetic and causal relationship between initiation or use of alcohol, caffeine, cannabis and nicotine.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide association study (GWAS) summary statistics from the UK Biobank, International Cannabis Consortium, and GWAS & Sequencing Consortium of Alcohol and Nicotine use.
METHODS NlmCategory: METHODS
Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide association study (GWAS) summary statistics from the UK Biobank, International Cannabis Consortium, and GWAS & Sequencing Consortium of Alcohol and Nicotine use. We obtained GWAS summary statistics from the aforementioned consortia for ten substance use traits including various measures of alcohol consumption, caffeine consumption, cannabis initiation and smoking behaviours. We then conducted SNP-heritability (h ) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs.
RESULTS NlmCategory: RESULTS
Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide association study (GWAS) summary statistics from the UK Biobank, International Cannabis Consortium, and GWAS & Sequencing Consortium of Alcohol and Nicotine use. We obtained GWAS summary statistics from the aforementioned consortia for ten substance use traits including various measures of alcohol consumption, caffeine consumption, cannabis initiation and smoking behaviours. We then conducted SNP-heritability (h ) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs. SNP h of the ten traits ranged from 0.03 to 0.11. After multiple testing correction, 29 of the 45 trait pairs showed evidence of being genetically correlated. MR analyses revealed that most SU traits were not causally associated with each other. However, we found evidence for an MR association between regular smoking initiation and caffeine consumption 40.17 mg; 95 % CI: [24.01, 56.33] increase in caffeine intake per doubling of odds in smoking initiation). Our findings were robust against horizontal pleiotropy, SNP-outliers, and the direction of causality was consistent in all MR analyses.
CONCLUSIONS NlmCategory: CONCLUSIONS
Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide association study (GWAS) summary statistics from the UK Biobank, International Cannabis Consortium, and GWAS & Sequencing Consortium of Alcohol and Nicotine use. We obtained GWAS summary statistics from the aforementioned consortia for ten substance use traits including various measures of alcohol consumption, caffeine consumption, cannabis initiation and smoking behaviours. We then conducted SNP-heritability (h ) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs. SNP h of the ten traits ranged from 0.03 to 0.11. After multiple testing correction, 29 of the 45 trait pairs showed evidence of being genetically correlated. MR analyses revealed that most SU traits were not causally associated with each other. However, we found evidence for an MR association between regular smoking initiation and caffeine consumption 40.17 mg; 95 % CI: [24.01, 56.33] increase in caffeine intake per doubling of odds in smoking initiation). Our findings were robust against horizontal pleiotropy, SNP-outliers, and the direction of causality was consistent in all MR analyses. Most of the substance traits were genetically correlated but there is little evidence to establish causality apart from the relationship between smoking initiation and caffeine consumption.
Copyright 2020 Elsevier B.V. All rights reserved.
DATE PUBLISHED
2020 Mar 20
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2020/01/20
revised 2020/03/06
accepted 2020/03/12
pubmed 2020/04/11 06:00
medline 2020/04/11 06:00
entrez 2020/04/11 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Chang LH Chang Lun-Hsien LH Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia. Electronic address: lun-hsien.chang@qimrberghofer.edu.au.
Ong JS Ong Jue-Sheng JS Statistical Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia. Electronic address: JueSheng.Ong@qimrberghofer.edu.au.
An J An Jiyuan J Statistical Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia. Electronic address: jiyuan.an@qimrberghofer.edu.au.
Verweij KJH Verweij Karin J H KJH Department of Psychiatry, Amsterdam UMC Location AMC, University of Amsterdam, Meibergdreef 5, 1105 AZ, Amsterdam, the Netherlands. Electronic address: karin.verweij@amsterdamumc.nl.
Vink JM Vink Jacqueline M JM Behavioural Science Institute, Developmental Psychopathology, Radboud University, Postbus 9104 6500 HE Nijmegen, the Netherlands. Electronic address: J.Vink@pwo.ru.nl.
Pasman J Pasman Joëlle J Behavioural Science Institute, Developmental Psychopathology, Radboud University, Postbus 9104 6500 HE Nijmegen, the Netherlands. Electronic address: j.pasman@bsi.ru.nl.
Liu M Liu Mengzhen M Institute for Behavioural Genetics, University of Colorado, Boulder, CO, 80309-0447, United States. Electronic address: mengzhen.liu@colorado.edu.
MacGregor S MacGregor Stuart S Statistical Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia. Electronic address: Stuart.MacGregor@qimrberghofer.edu.au.
Cornelis MC Cornelis Marilyn C MC Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N Lake Shore Dr Suite 1400, Chicago, IL, 60611, United States. Electronic address: marilyn.cornelis@northwestern.edu.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia. Electronic address: Nick.Martin@qimrberghofer.edu.au.
Derks EM Derks Eske M EM Translational Neurogenomics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia. Electronic address: Eske.Derks@qimrberghofer.edu.au.
INVESTIGATORS
JOURNAL
VOLUME: 210
ISSUE:
TITLE: Drug and alcohol dependence
ISOABBREVIATION: Drug Alcohol Depend
YEAR: 2020
MONTH: Mar
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1879-0046
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Drug Alcohol Depend
COUNTRY: Ireland
ISSNLINKING: 0376-8716
NLMUNIQUEID: 7513587
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Coffee
Genetic instruments
Single nucleotide polymorphism
Substance use
Tea
Tobacco
Two-sample Mendelian randomisation
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's