Genome-wide association analysis of opioid use disorder: A novel approach using clinical data.
paper
Cited
Public
- Authors
- Song, Wenyu; Kossowsky, Joe; Torous, John; Chen, Chia-Yen; Huang, Hailiang; Mukamal, Kenneth J; Berde, Charles B; Bates, David W; Wright, Adam
- Year
- 2020
- Journal
- Drug and alcohol dependence
- PMID
- 32961455
- DOI
- 10.1016/j.drugalcdep.2020.108276
- PMCID
- PMC7736461
BACKGROUND: Opioid use disorder (OUD) represents a large and pervasive global public health challenge. Previous genetic studies have demonstrated the significant heritability of OUD and identified several single-nucleotide polymorphisms (SNPs) associated with its prevalence. METHODS: In this paper, we conducted a genome-wide association analysis on opioid use disorder that leveraged genetic and clinical data contained in a biobank of 21,310 patients of European ancestry. We identified 1039 cases of opioid use disorder based on diagnostic codes from nearly 16 million encounters in electronic health records (EHRs). RESULTS: We discovered one novel OUD-associated locus on chromosome 4 that was significant at a genome-wide threshold (p = 2.40 × 10). Heritability analysis suggested that common SNPs explained 0.06 (se 0.02, p = 0.0065) of the phenotypic variation in OUD. When we restricted controls to those with previous opioid prescriptions, we were able to further strengthen the original signal and discovered another significant locus on chromosome 16. Pair-wise genetic correlation analysis yielded strong positive correlations between OUD and two other major substance use disorders, alcohol and nicotine, with the strongest correlation between nicotine and opioid use disorder (genetic correlation 0.65, se = 0.19, p = 0.00048), suggesting a significant shared genetic component across different substance disorders. CONCLUSIONS: This pragmatic, clinically-focused approach may supplement more traditional methods to facilitate identification of new genetic underpinnings of OUD and related disorders.
Manhattan plot from genome-wide association study for opioid use disorder A. whole controlB. opioid exposed control
Regional plot
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| Name | Type |
|---|---|
| 1000 Genomes Project | cohort |
| addiction | phenotype |
| African American | cohort |
| alcohol | phenotype |
| Alcohol Traits local | phenotype |
| Alcohol Use Disorder | phenotype |
| Alzheimer's disease | phenotype |
| Amphetamine use disorder | phenotype |
| Australia | cohort |
| autosomal biallelic SNPs | cohort |
| biobanks | cohort |
| cannabis use disorder | phenotype |
| case cohort | cohort |
| chronic pain | phenotype |
| claims-identified cases local | cohort |
| Clinical Biobank local | cohort |
| clinical phenotype information local | phenotype |
| Cnih3 | gene |
| cocaine use disorder | phenotype |
| control group | cohort |
| controls | cohort |
| DEFB131 local | gene |
| depressive symptoms | phenotype |
| EHR-derived patient prescription data local | cohort |
| EHR-derived phenotypes local | phenotype |
| electronic health records | cohort |
| European ancestry | cohort |
| European population | cohort |
| exposed-control analysis local | cohort |
| Exposed Patients local | cohort |
| gout local | phenotype |
| GWAS & Sequencing Consortium of Alcohol and Nicotine use | cohort |
| Harvard-affiliated hospitals local | cohort |
| hydrocodone | drug |
| Illumina Multi-Ethnic Global (MEG) array local | drug |
| immune function | phenotype |
| insomnia | phenotype |
| Kcnc1 | gene |
| KCNG2 | gene |
| Large Integrated Health Care System local | cohort |
| LD Hub | cohort |
| Long-term opioid use disorder local | phenotype |
| Major substance use disorder local | phenotype |
| MEGA | drug |
| MEGA Ex local | drug |
| Michigan Imputation Server | drug |
| mood disorders | phenotype |
| nicotine | drug |
| nicotine use disorder | phenotype |
| Non-European-Americans local | cohort |
| Novel Genomic Locus 1 local | variant |
| Novel Genomic Locus 2 local | variant |
| opioid | drug |
| opioid dependence | phenotype |
| opioid exposed controls local | cohort |
| Opioid-exposed controls local | cohort |
| opioid overdose | phenotype |
| Opioid Receptor Binding local | phenotype |
| Opioid-related deaths local | phenotype |
| OPRM1 | cohort |
| OUD | phenotype |
| overall control group local | cohort |
| oxycodone | drug |
| Pain Phenotype local | phenotype |
| pain phenotypes | phenotype |
| Partners Biobank local | cohort |
| Partners Healthcare System Biobank local | cohort |
| Patient Billing Data local | cohort |
| personality traits | phenotype |
| Polimanti 2020 opioid dependence cohort (European ancestry) local | cohort |
| Polimanti Study Results local | cohort |
| Research populations local | cohort |
| RGMA | gene |
| RP11-1396O13.13 local | gene |
| rs10014685 | variant |
| rs114237113 local | variant |
| rs12596025 local | variant |
| rs12931235 local | variant |
| rs2001392 local | variant |
| rs3778150 | variant |
| SHAPEIT2 | drug |
| SLC2A9 local | gene |
| SLC30A9 local | gene |
| smoking | phenotype |
| SNP | cohort |
| SNP_chr4 local | variant |
| study cohort | cohort |
| substance abuse | phenotype |
| substance use | phenotype |
| Substance Use Disorder phenotype local | phenotype |
| Un-exposed Control Group local | cohort |
| unexposed controls | cohort |
| United States | cohort |
| ZNF518B local | gene |
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