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Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry.

ABSTRACT: The growing prevalence of opioid use disorder (OUD) constitutes an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using prescription opioids 'not as prescribed'. We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU) in 23andMe research participants of European ancestry (N = 132,113; 21% cases). We identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near LRRIQ3). POU showed positive genetic correlations with the two largest available GWAS of OUD and opioid dependence (r_g = 0.64, 0.80, respectively). We also identified numerous additional genetic correlations with POU, including alcohol dependence (r_g = 0.74), smoking initiation (r_g = 0.63), pain relief medication intake (r_g = 0.49), major depressive disorder (r_g = 0.44), chronic pain (r_g = 0.42), insomnia (r_g = 0.39), and loneliness (r_g = 0.28). Although POU was positively genetically correlated with risk-taking (r_g = 0.38), conditioning POU on risk-taking did not substantially alter the magnitude or direction of these genetic correlations, suggesting that POU does not simply reflect a genetic tendency towards risky behavior. Lastly, we performed phenome- and lab-wide association analyses, which uncovered additional phenotypes that were associated with POU, including respiratory failure, insomnia, ischemic heart disease, and metabolic and blood-related biomarkers. We conclude that opioid misuse can be measured in population-based cohorts and provides a cost-effective complementary strategy for understanding the genetic basis of OUD.

SUBMITTER: Sanchez-Roige S

PROVIDER: S-EPMC8562028 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceBetween 1997 and 2017, the United States saw increases in nonmedical prescription opioid use and its consequences, as well as changes in marijuana policies. Ecological-level research hypothesized that medical marijuana legalization may reduce prescription opioid use by allowing medical marijuana as an alternative.ObjectivesTo investigate the association of state-level medical marijuana law enactment with individual-level nonmedical prescription opioid use and prescription opioid use disorder among prescription opioid users and to determine whether these outcomes varied by age and racial/ethnic groups.Design, setting, and participantsThis cross-sectional study used restricted data on 627 000 individuals aged 12 years and older from the 2004 to 2014 National Survey on Drug Use and Health, a population-based survey representative of the civilian population of the United States. Analyses were completed from March 2018 to May 2018.ExposuresTime-varying indicator of state-level medical marijuana law enactment (0 = never law enactment, 1 = before law enactment, and 2 = after law enactment).Main outcomes and measuresPast-year nonmedical prescription opioid use and prescription opioid use disorder among prescription opioid users. Odds ratios of nonmedical prescription opioid use and prescription opioid use disorder comparing the period before and after law enactment were presented overall, by age and racial/ethnic group, and adjusted for individual- and state-level confounders.ResultsThe study sample included 627 000 participants (51.51% female; 9.88% aged 12-17 years, 13.30% aged 18-25 years, 14.30% aged 26-34 years, 25.02% aged 35-49 years, and 37.50% aged ≥50 years; the racial/ethnic distribution was 66.97% non-Hispanic white, 11.83% non-Hispanic black, 14.47% Hispanic, and 6.73% other). Screening and interview response rates were 82% to 91% and 71% to 77%, respectively. Overall, there were small changes in nonmedical prescription opioid use prevalence after medical marijuana law enactment (4.32% to 4.86%; adjusted odds ratio, 1.13; 95% CI, 1.06-1.20). Prescription opioid use disorder prevalence among prescription opioid users decreased slightly after law enactment, but the change was not statistically significant (15.41% to 14.76%; adjusted odds ratio, 0.95; 95% CI, 0.81-1.11). Outcomes were similar when stratified by age and race/ethnicity.Conclusions and relevanceThis study found little evidence of an association between medical marijuana law enactment and nonmedical prescription opioid use or prescription opioid use disorder among prescription opioid users. Further research should disentangle the potential mechanisms through which medical marijuana laws may reduce opioid-related harm.

Project description:The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.

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Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry.

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