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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31731259
TITLE
Associations between polygenic risk for tobacco and alcohol use and liability to tobacco and alcohol use, and psychiatric disorders in an independent sample of 13,999 Australian adults.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Substance use, substance use disorders (SUDs), and psychiatric disorders commonly co-occur. Genetic risk common to these complex traits is an important explanation; however, little is known about how polygenic risk for tobacco or alcohol use overlaps the genetic risk for the comorbid SUDs and psychiatric disorders.
METHODS NlmCategory: METHODS
Substance use, substance use disorders (SUDs), and psychiatric disorders commonly co-occur. Genetic risk common to these complex traits is an important explanation; however, little is known about how polygenic risk for tobacco or alcohol use overlaps the genetic risk for the comorbid SUDs and psychiatric disorders. We constructed polygenic risk scores (PRSs) using GWAS meta-analysis summary statistics from a large discovery sample, GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN), for smoking initiation (SI; N = 631,564), age of initiating regular smoking (AI; N = 258,251), cigarettes per day (CPD; N = 258,999), smoking cessation (SC; N = 312,273), and drinks per week (DPW; N = 527,402). We then estimated the fixed effect of these PRSs on the liability to 15 phenotypes related to tobacco and alcohol use, substance use disorders, and psychiatric disorders in an independent target sample of Australian adults.
RESULTS NlmCategory: RESULTS
Substance use, substance use disorders (SUDs), and psychiatric disorders commonly co-occur. Genetic risk common to these complex traits is an important explanation; however, little is known about how polygenic risk for tobacco or alcohol use overlaps the genetic risk for the comorbid SUDs and psychiatric disorders. We constructed polygenic risk scores (PRSs) using GWAS meta-analysis summary statistics from a large discovery sample, GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN), for smoking initiation (SI; N = 631,564), age of initiating regular smoking (AI; N = 258,251), cigarettes per day (CPD; N = 258,999), smoking cessation (SC; N = 312,273), and drinks per week (DPW; N = 527,402). We then estimated the fixed effect of these PRSs on the liability to 15 phenotypes related to tobacco and alcohol use, substance use disorders, and psychiatric disorders in an independent target sample of Australian adults. After adjusting for multiple testing, 10 of 75 combinations of discovery and target phenotypes remained significant. PRS-SI (R range: 1.98%-5.09 %) was positively associated with SI, DPW, and with DSM-IV and FTND nicotine dependence, and conduct disorder. PRS-AI (R : 3.91 %) negatively associated with DPW. PRS-CPD (R : 1.56 %-1.77 %) positively associated with DSM-IV nicotine dependence and conduct disorder. PRS-DPW (R : 3.39 %-6.26 %) positively associated with only DPW. The variation of DPW was significantly influenced by sex*PRS-SI, sex*PRS-AI and sex*PRS-DPW. Such interaction effect was not detected in the other 14 phenotypes.
CONCLUSIONS NlmCategory: CONCLUSIONS
Substance use, substance use disorders (SUDs), and psychiatric disorders commonly co-occur. Genetic risk common to these complex traits is an important explanation; however, little is known about how polygenic risk for tobacco or alcohol use overlaps the genetic risk for the comorbid SUDs and psychiatric disorders. We constructed polygenic risk scores (PRSs) using GWAS meta-analysis summary statistics from a large discovery sample, GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN), for smoking initiation (SI; N = 631,564), age of initiating regular smoking (AI; N = 258,251), cigarettes per day (CPD; N = 258,999), smoking cessation (SC; N = 312,273), and drinks per week (DPW; N = 527,402). We then estimated the fixed effect of these PRSs on the liability to 15 phenotypes related to tobacco and alcohol use, substance use disorders, and psychiatric disorders in an independent target sample of Australian adults. After adjusting for multiple testing, 10 of 75 combinations of discovery and target phenotypes remained significant. PRS-SI (R range: 1.98%-5.09 %) was positively associated with SI, DPW, and with DSM-IV and FTND nicotine dependence, and conduct disorder. PRS-AI (R : 3.91 %) negatively associated with DPW. PRS-CPD (R : 1.56 %-1.77 %) positively associated with DSM-IV nicotine dependence and conduct disorder. PRS-DPW (R : 3.39 %-6.26 %) positively associated with only DPW. The variation of DPW was significantly influenced by sex*PRS-SI, sex*PRS-AI and sex*PRS-DPW. Such interaction effect was not detected in the other 14 phenotypes. Polygenic risks associated with tobacco use are also associated with liability to alcohol consumption, nicotine dependence, and conduct disorder.
Copyright 2019 Elsevier B.V. All rights reserved.
DATE PUBLISHED
2019 Nov 02
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/05/27
revised 2019/09/18
accepted 2019/10/21
entrez 2019/11/16 06:00
pubmed 2019/11/16 06:00
medline 2019/11/16 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, Herston QLD 4006, Australia; Faculty of Medicine, the University of Queensland, 20 Weightman St, Herston QLD 4006, Australia. Electronic address: lun-hsien.chang@qimrberghofer.edu.au.
Whitfield JB Whitfield John B JB Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia. Electronic address: John.Whitfield@qimrberghofer.edu.au.
Liu M Liu Mengzhen M Department of Psychology, University of Minnesota Twin Cities, 75 E River Rd, Minneapolis, MN 55455, USA. Electronic address: mengzhen.liu@colorado.edu.
Medland SE Medland Sarah E SE Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia. Electronic address: Sarah.Medland@qimrberghofer.edu.au.
Hickie IB Hickie Ian B IB Brain and Mind Centre, University of Sydney, 94 Mallett St, Camperdown NSW 2050, USA. Electronic address: ian.hickie@sydney.edu.au.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia. Electronic address: Nick.Martin@qimrberghofer.edu.au.
Verhulst B Verhulst Brad B Department of psychology, Michigan State University, 316 Physics Road #262, East Lansing, MI 48824, USA. Electronic address: bverhuls@msu.edu.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA. Electronic address: heatha@psychiatry.wustl.edu.
Madden PA Madden Pamela A PA Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA. Electronic address: pam@matlock.wustl.edu.
Statham DJ Statham Dixie J DJ School of Health and Life Sciences, Federation University, Federation University Australia, PO Box 663, Ballarat, VIC 3353, Australia. Electronic address: d.statham@federation.edu.au.
Gillespie NA Gillespie Nathan A NA Virginia Institute for Psychiatric and Behavioural Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: Nathan.Gillespie@vcuhealth.org.
GSCAN Consortium
INVESTIGATORS
JOURNAL
VOLUME: 205
ISSUE:
TITLE: Drug and alcohol dependence
ISOABBREVIATION: Drug Alcohol Depend
YEAR: 2019
MONTH: Nov
DAY: 02
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
Alcohol dependence
Conduct disorder
Genetics
Genotype by sex interaction
Nicotine dependence
Polygenic risk score
Twins
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's