A systematic review of GWAS identified SNPs associated with outcomes of medications for opioid use disorder.

BACKGROUND: Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes. OBJECTIVES: This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved. METHODS: Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively. RESULTS: Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10-7. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese. LIMITATIONS: The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model. CONCLUSION: The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.

GWAS-identified genetic variants associated with medication-assisted treatment outcomes in patients with opioid use disorder: a systematic review and meta-analysis protocol.

BACKGROUND: The burden of opioid use disorder (OUD) has been increasing in North America. Administration of medication-assisted treatments (MATs) for OUD on an individual-dose basis has been shown to affect patient responses to treatment, proving to be, on occasion, dangerous. A genetic basis has been identified for some MAT responses in a candidate gene context, but consensus has not been reached for any genome-wide significant associations. This systematic review aims to identify and assess any genetic variants associated with MAT patient outcomes at genome-wide significance. METHODS: The databases searched by the authors will be: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog, GWAS Central, and NIH Database of Genotypes and Phenotypes. A title and abstract screening, full-text screening, data extraction, and quality assessment will be completed in duplicate for each study via Covidence. Treatment outcomes of interest include continued opioid use or abstinence during treatment or at follow-up, time to relapse, treatment retention rates, opioid overdose, other substance use, comorbid psychiatric disorders, risk taking behaviors, MAT plasma concentrations, and mortality rates. Analysis methods applied, if appropriate, will include random effects meta-analysis with pooled odds ratios for all outcomes. Subgroup analyses will also be implemented, when possible. DISCUSSION: This systematic review can hopefully inform the direction of future research, aiding in the development of a safer and more patient-centered treatment. It will be able to highlight genome-wide significant variants that are replicable and associated with MAT patient outcomes. SYSTEMATIC REVIEW REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration ID CRD42020169121).