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| PMID |
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| TITLE |
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| 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. |
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| ABSTRACT |
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| BACKGROUND |
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| 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 |
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| 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 |
|
| 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 |
|
| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2019/05/27 |
| revised |
2019/09/18 |
| accepted |
2019/10/21 |
| pubmed |
2019/11/16 06:00 |
| medline |
2020/06/24 06:00 |
| entrez |
2019/11/16 06:00 |
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| AUTHORS |
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| 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 |
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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 |
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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. |
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GSCAN Consortium |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 205 |
| ISSUE: |
| TITLE: Drug and alcohol dependence |
| ISOABBREVIATION: Drug Alcohol Depend |
| YEAR: 2019 |
| MONTH: 12 |
| DAY: 01 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1879-0046 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Drug Alcohol Depend |
| COUNTRY: Ireland |
| ISSNLINKING: 0376-8716 |
| NLMUNIQUEID: 7513587 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
| Twin Study |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| Alcohol dependence |
| Conduct disorder |
| Genetics |
| Genotype by sex interaction |
| Nicotine dependence |
| Polygenic risk score |
| Twins |
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| MESH HEADINGS |
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| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
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| Adult |
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| Alcohol Drinking |
genetics |
| Alcoholism |
genetics |
| Australia |
epidemiology |
| Diagnostic and Statistical Manual of Mental Disorders |
epidemiology |
| Female |
epidemiology |
| Humans |
epidemiology |
| Male |
epidemiology |
| Mental Disorders |
genetics |
| Middle Aged |
genetics |
| Multifactorial Inheritance |
genetics |
| Risk Factors |
genetics |
| Tobacco Use |
genetics |
| Tobacco Use Disorder |
genetics |
| Young Adult |
genetics |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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