Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry
Year: 2021
Type: article
Study design: Observational Study
Abstract: 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 a positive genetic correlation with the largest available GWAS of opioid dependence and OUD (rg=0.64-0.80). We also identified numerous additional genetic correlations with POU, including alcohol dependence (rg=0.74), smoking initiation (rg=0.63), pain relief medication intake (rg=0.49), major depressive disorder (rg=0.44), chronic pain (rg=0.42), insomnia (rg=0.39), and loneliness (rg=0.28). Although POU was positively genetically correlated with risk-taking (rg=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.
Source: Molecular Psychiatry
Authors: Sandra Sanchez-Roige, Pierre Fontanillas, Mariela V. Jennings, Sevim B. Bianchi, Yuye Huang, Alexander S. Hatoum, Julia Sealock, Lea K. Davis, Sarah L. Elson, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Nicholas A. Furlotte, David A. Hinds, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A. M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, Catherine H. Wilson, Abraham A. Palmer
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: U.S. Department of Health and Human Services, Tobacco-Related Disease Research Program, Vanderbilt University, Vanderbilt University Medical Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, H2020 European Research Council
Awards: G1083756078, G1278019779, G134791383, G1429306515, G1435936284, G1438427666, G1531600799, G1766209448, G1846282300, G1950110545, G1967470738, G2103760183, G2195549334, Understanding the genetic risk underlying racial disparities in uterine fibroids, G2310098089, G2328519459, G2382761143, G2481876672, G25420283, G2615776415, G2683268942, G2745671074, G2998239322, G3337018014, G335750049, G3395468139, G3420921512, Mental health and chronic disease: A psycheMERGE investigation into the shared biology underlying psychiatric disorders and their physical comorbidities, G3543852751, G3619590958, G3639572947, G364208108, G3791753988, G3938985443, G4049315607, G4198746417, G4395870004, G4410787187, G4558225130, Measuring Depression: Using biomarkers to investigate the biology of depression, G4814458579, G4880665887, G5184311545, G560889077, G5679716143, G5717004637, The molecular genetic architecture of educational attainment and its significance for cognitive health, Genetic Epidemiology of Multiple Sclerosis, G6173849340, G6589054092, G6624680524, G7163342664, G7349708091, Biomedical Research Training in Drug Abuse, The Vanderbilt Institute for Clinical and Translational Research (VICTR), PsycheMERGE: Leveraging electronic health records and genomics for mental health research, G8011460706, Discovering Biology for Neuropsychiatric Diseases Through Omics Studies on Comorbidities, G8098630230, G8229893880, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8332127685, Center for Genetic Studies of Drug Abuse in Outbred Rats, G8603512441, G9000002232, G9000008449, G9000022789, G9000025954, G9000039033, G9000040245, G9000041532, G9000043901, G9000054231, G9000090229, G9000167145, G9000273886, G949362299, G95160140
OpenAlex ID: W3209599011