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

Caroul Chawar; Alannah Hillmer; Stephanie Sanger; Alessia D'Elia; Balpreet Panesar; Lucy Guan; Dave Xiaofei Xie; Nandini Bansal; Aamna Abdullah; Flavio Kapczinski; Guillaume Pare; Lehana Thabane; Zainab Samaan

doi:10.1186/s13722-021-00278-y

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

Addict Sci Clin Pract. 2021 Nov 27;16(1):70. doi: 10.1186/s13722-021-00278-y.

Authors

Caroul Chawar^{1

2}, Alannah Hillmer^{1

2}, Stephanie Sanger³, Alessia D'Elia^{1

2}, Balpreet Panesar^{1

2}, Lucy Guan^{2

4}, Dave Xiaofei Xie^{2

4}, Nandini Bansal^{2

4}, Aamna Abdullah^{2

4}, Flavio Kapczinski², Guillaume Pare^{5

6}, Lehana Thabane^{5

6

7}, Zainab Samaan⁸

Affiliations

¹ Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.
² Department of Psychiatry and Behavioural Neurosciences, St. Joseph's Healthcare Hamilton, 100 West 5th St., Hamilton, ON, L8N3K7, Canada.
³ Health Sciences Library, McMaster University, Hamilton, ON, Canada.
⁴ Health Sciences Program, McMaster University, Hamilton, ON, Canada.
⁵ Population Health Research Institute, Hamilton, ON, Canada.
⁶ Department of Health Research Method, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
⁷ Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
⁸ Department of Psychiatry and Behavioural Neurosciences, St. Joseph's Healthcare Hamilton, 100 West 5th St., Hamilton, ON, L8N3K7, Canada. samaanz@mcmaster.ca.

Abstract

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.

Keywords: GWAS; MOUD; Methadone; Opioid; Pharmacogenetic; Systematic review.

Publication types

Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Buprenorphine* / therapeutic use
Calcium-Calmodulin-Dependent Protein Kinases / therapeutic use
Eye Proteins / therapeutic use
Genome-Wide Association Study
Humans
Methadone / therapeutic use
Opiate Substitution Treatment
Opioid-Related Disorders* / drug therapy
Opioid-Related Disorders* / genetics
Polymorphism, Single Nucleotide / genetics

Substances

EYS protein, human
Eye Proteins
Buprenorphine
Calcium-Calmodulin-Dependent Protein Kinases
TRIB2 protein, human
Methadone

Grants and funding

PJT-156306/CIHR/Canada