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Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- 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=7.2×10−8). 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=1.68×10−8). 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=2.9×10−8) and a significant association with musculoskeletal disorders in the UK Biobank (p=4.88×10−7). 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=8.1×10−5; OD cases vs. exposed controls, p=0.054) and OE (exposed controls vs. unexposed controls, p=3.6×10−5). A PRS based on a GWAS of neuroticism (N=390,278) was positively associated with OD (OD cases vs. unexposed controls, p=3.2×10−5; 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.
- Subjects :
- Oncology
0303 health sciences
medicine.medical_specialty
business.industry
Opioid use
Significant difference
Genomics
Genome-wide association study
medicine.disease
Neuroticism
3. Good health
03 medical and health sciences
0302 clinical medicine
Opioid
Schizophrenia
Internal medicine
medicine
Polygenic risk score
business
030217 neurology & neurosurgery
030304 developmental biology
medicine.drug
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....e4b52b0af00762e9cd09073185e7ff8b