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
30875648
TITLE
Association between polygenic risk for tobacco or alcohol consumption and liability to licit and illicit substance use in young Australian adults.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Co-morbid substance use is very common. Despite a historical focus using genetic epidemiology to investigate comorbid substance use and misuse, few studies have examined substance-substance associations using polygenic risk score (PRS) methods.
METHODS NlmCategory: METHODS
Co-morbid substance use is very common. Despite a historical focus using genetic epidemiology to investigate comorbid substance use and misuse, few studies have examined substance-substance associations using polygenic risk score (PRS) methods. Using summary statistics from the largest substance use GWAS to date (258,797- 632,802 subjects), GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), we constructed PRSs for smoking initiation (PRS-SI), age of initiation of regular smoking (PRS-AI), cigarettes per day (PRS-CPD), smoking cessation (PRS-SC), and drinks per week (PRS-DPW). We then estimated the fixed effect of individual PRSs on 22 lifetime substance use and substance use disorder phenotypes collected in an independent sample of 2463 young Australian adults using genetic restricted maximal likelihood (GREML) in Genome-wide Complex Trait Analysis (GCTA), separately in females, males and both sexes together.
RESULTS NlmCategory: RESULTS
Co-morbid substance use is very common. Despite a historical focus using genetic epidemiology to investigate comorbid substance use and misuse, few studies have examined substance-substance associations using polygenic risk score (PRS) methods. Using summary statistics from the largest substance use GWAS to date (258,797- 632,802 subjects), GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), we constructed PRSs for smoking initiation (PRS-SI), age of initiation of regular smoking (PRS-AI), cigarettes per day (PRS-CPD), smoking cessation (PRS-SC), and drinks per week (PRS-DPW). We then estimated the fixed effect of individual PRSs on 22 lifetime substance use and substance use disorder phenotypes collected in an independent sample of 2463 young Australian adults using genetic restricted maximal likelihood (GREML) in Genome-wide Complex Trait Analysis (GCTA), separately in females, males and both sexes together. After accounting for multiple testing, PRS-SI significantly explained variation in the risk of cocaine (0.67%), amphetamine (1.54%), hallucinogens (0.72%), ecstasy (1.66%) and cannabis initiation (0.97%), as well as DSM-5 alcohol use disorder (0.72%). PRS-DPW explained 0.75%, 0.59% and 0.90% of the variation of cocaine, amphetamine and ecstasy initiation respectively. None of the 22 phenotypes including emergent classes of substance use were significantly predicted by PRS-AI, PRS-CPD, and PRS-SC.
CONCLUSIONS NlmCategory: CONCLUSIONS
Co-morbid substance use is very common. Despite a historical focus using genetic epidemiology to investigate comorbid substance use and misuse, few studies have examined substance-substance associations using polygenic risk score (PRS) methods. Using summary statistics from the largest substance use GWAS to date (258,797- 632,802 subjects), GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), we constructed PRSs for smoking initiation (PRS-SI), age of initiation of regular smoking (PRS-AI), cigarettes per day (PRS-CPD), smoking cessation (PRS-SC), and drinks per week (PRS-DPW). We then estimated the fixed effect of individual PRSs on 22 lifetime substance use and substance use disorder phenotypes collected in an independent sample of 2463 young Australian adults using genetic restricted maximal likelihood (GREML) in Genome-wide Complex Trait Analysis (GCTA), separately in females, males and both sexes together. After accounting for multiple testing, PRS-SI significantly explained variation in the risk of cocaine (0.67%), amphetamine (1.54%), hallucinogens (0.72%), ecstasy (1.66%) and cannabis initiation (0.97%), as well as DSM-5 alcohol use disorder (0.72%). PRS-DPW explained 0.75%, 0.59% and 0.90% of the variation of cocaine, amphetamine and ecstasy initiation respectively. None of the 22 phenotypes including emergent classes of substance use were significantly predicted by PRS-AI, PRS-CPD, and PRS-SC. To our knowledge, this is the first study to report significant genetic overlap between the polygenic risks for smoking initiation and alcohol consumption and the risk of initiating major classes of illicit substances. PRSs constructed from large discovery GWASs allows the detection of novel genetic associations.
Copyright 2019 Elsevier B.V. All rights reserved.
DATE PUBLISHED
2019 Feb 16
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/10/06
revised 2018/12/25
accepted 2019/01/19
pubmed 2019/03/16 06:00
medline 2019/03/16 06:00
entrez 2019/03/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Chang LH Chang Lun-Hsien LH Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Faculty of Medicine, the University of Queensland, Brisbane, Australia. Electronic address: Lun-Hsien.Chang@qimrberghofer.edu.au.
Couvy-Duchesne B Couvy-Duchesne Baptiste B Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Institute for Molecular Bioscience, the University of Queensland, Brisbane, Australia.
Liu M Liu Mengzhen M Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Medland SE Medland Sarah E SE Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Verhulst B Verhulst Brad B Department of Psychology, Michigan State University, East Lansing, MI, USA.
Benotsch EG Benotsch Eric G EG Psychology Department, Virginia Commonwealth University, VA, USA.
Hickie IB Hickie Ian B IB Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Gillespie NA Gillespie Nathan A NA Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Department of Psychology, Michigan State University, East Lansing, MI, USA.
GSCAN Consortium
INVESTIGATORS
JOURNAL
VOLUME: 197
ISSUE:
TITLE: Drug and alcohol dependence
ISOABBREVIATION: Drug Alcohol Depend
YEAR: 2019
MONTH: Feb
DAY: 16
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
Addiction
Genetics
Polygenic risk
Twins
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's