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
31936517
TITLE
Genome-Wide Association Study of Opioid Cessation.
ABSTRACT
The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in ( = 2.24 × 10 ), rs36098404 in ( = 2.24 × 10 ), and rs592026 in ( = 6.53 × 10 ). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism ( = 3.79 × 10 ) and fibroblast growth factor (FGF) signaling ( = 2.39 × 10 ). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.
DATE PUBLISHED
2020 Jan 09
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/12/09
revised 2019/12/20
accepted 2020/01/03
entrez 2020/01/16 06:00
pubmed 2020/01/16 06:00
medline 2020/01/16 06:01
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cox JW Cox Jiayi W JW Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02118, USA.
Sherva RM Sherva Richard M RM Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02118, USA.
Lunetta KL Lunetta Kathryn L KL Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Johnson EC Johnson Emma C EC Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Martin NG Martin Nicholas G NG School of Psychology, The University of Queensland, St Lucia QLD 4072, Australia.
Degenhardt L Degenhardt Louisa L School of Medicine, University of New South Wales, Sydney NSW 2052, Australia.
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA.
Kranzler HR Kranzler Henry R HR Perelman School of Medicine, University of Pennsylvania and VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA 19104, USA.
Gelernter J Gelernter Joel J Department of Psychiatry, VA CT Healthcare Center, West Haven, CT 06516, USA.
Farrer LA Farrer Lindsay A LA Departments of Neurology, Ophthalmology and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA 02118, USA.
INVESTIGATORS
JOURNAL
VOLUME: 9
ISSUE: 1
TITLE: Journal of clinical medicine
ISOABBREVIATION: J Clin Med
YEAR: 2020
MONTH: Jan
DAY: 09
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 2077-0383
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: J Clin Med
COUNTRY: Switzerland
ISSNLINKING: 2077-0383
NLMUNIQUEID: 101606588
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
RC2 DA028909 NIDA NIH HHS United States
R01 DA12690 NIDA NIH HHS United States
R01 DA12849 NIDA NIH HHS United States
R01 DA18432, NIDA NIH HHS United States
R01 AA11330 NIAAA NIH HHS United States
R01 AA017535 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
genome-wide association study
opioid cessation
opioid use disorder
polygenic risk score
shared genetic risk
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's