In:
Molecular Psychiatry, Springer Science and Business Media LLC, Vol. 26, No. 11 ( 2021-11), p. 6209-6217
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.
Type of Medium:
Online Resource
ISSN:
1359-4184
,
1476-5578
DOI:
10.1038/s41380-021-01335-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
1502531-7
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