Browsing by Author "Stallings, Michael"

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    Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium
    (Springer Nature, 2020-08) Polimanti, Renato; Walters, Raymond K.; Johnson, Emma C.; McClintick, Jeanette N.; Adkins, Amy E.; Adkins, Daniel E.; Bacanu, Silviu-Alin; Bierut, Laura J.; Bigdeli, Tim B.; Brown, Sandra; Bucholz, Kathleen K.; Copeland, William E.; Costello, E. Jane; Degenhardt, Louisa; Farrer, Lindsay A.; Foroud, Tatiana M.; Fox, Louis; Goate, Alison M.; Grucza, Richard; Hack, Laura M.; Hancock, Dana B.; Hartz, Sarah M.; Heath, Andrew C.; Hewitt, John K.; Hopfer, Christian J.; Johnson, Eric O.; Kendler, Kenneth S.; Kranzler, Henry R.; Krauter, Kenneth; Lai, Dongbing; Madden, Pamela A.F.; Martin, Nicholas G.; Maes, Hermine H.; Nelson, Elliot C.; Peterson, Roseann E.; Porjesz, Bernice; Riley, Brien P.; Saccone, Nancy; Stallings, Michael; Wall, Tamara L.; Webb, Bradley T.; Wetherill, Leah; Biochemistry and Molecular Biology, School of Medicine
    To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.