|
PMID |
|
|
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 |
|
|
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 |
|
|
|