Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium
By
Renato Polimanti,
Raymond K Walters,
Emma C. Johnson,
Jeanette N. McClintick,
Amy E. Adkins,
Daniel E Adkins,
Silviu-Alin Bacanu,
Laura J. Bierut,
Tim B. Bigdeli,
Sandra Brown,
Kathy Bucholz,
William E. Copeland,
E. Jane Costello,
Louisa Degenhardt,
Lindsay A. Farrer,
Tatiana Foroud,
Louis Fox,
Alison M. Goate,
Richard Grucza,
Laura M. Hack,
Dana B. Hancock,
Sarah Hartz,
Andrew C. Heath,
John Hewitt,
Christian J. Hopfer,
Eric O. Johnson,
Kenneth S Kendler,
Henry R. Kranzler,
Ken Krauter,
Dongbing Lai,
Pamela A F Madden,
Nicholas G Martin,
Hermine H Maes,
Elliot C. Nelson,
Roseann E. Peterson,
Bernice Porjesz,
Brien P. Riley,
Nancy Saccone,
Michael Stallings,
Tamara Wall,
Bradley T. Webb,
Leah Wetherill the Psychiatric Genomics Consortium Substance Use Disorders Workgroup,
Howard J. Edenberg,
Arpana Agrawal,
Joel Gelernter
Posted 11 Sep 2019
bioRxiv DOI: 10.1101/765065
(published DOI: 10.1038/s41380-020-0677-9)
To provide novel insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing up to 4,503 OD cases, 4,173 opioid-exposed controls, and 32,500 opioid-unexposed controls. Among the variants identified, rs9291211 was associated with OE (a comparison of exposed vs. unexposed controls; z=-5.39, p=7.2x10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N>360,000) found association of this variant with propensity to use dietary supplements (p=1.68x10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (z=4.69, p=10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (z=5.55, p=2.9x10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p=4.88x10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (N=466,571) was positively associated with OD (OD cases vs. unexposed controls, p=8.1x10-5; OD cases vs. exposed controls, p=0.054) and OE (exposed controls vs. unexposed controls, p=3.6x10-5). A PRS based on a GWAS of neuroticism (N=390,278) was positively associated with OD (OD cases vs. unexposed controls, p=3.2x10-5; OD cases vs. exposed controls, p=0.002) but not with OE (p=0.671). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls (exposed vs. unexposed) in studies of addiction.
Download data
- Downloaded 675 times
- Download rankings, all-time:
- Site-wide: 32,310
- In genetics: 1,622
- Year to date:
- Site-wide: 34,638
- Since beginning of last month:
- Site-wide: 41,869
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!