Publications [#349056] of Elizabeth J. Costello

Journal Articles

1. Polimanti, R; Walters, RK; Johnson, EC; McClintick, JN; Adkins, AE; Adkins, DE; Bacanu, S-A; Bierut, LJ; Bigdeli, TB; Brown, S; Bucholz, KK; Copeland, WE; Costello, EJ; Degenhardt, L; Farrer, LA; Foroud, TM; Fox, L; Goate, AM; Grucza, R; Hack, LM; Hancock, DB; Hartz, SM; Heath, AC; Hewitt, JK; Hopfer, CJ; Johnson, EO; Kendler, KS; Kranzler, HR; Krauter, K; Lai, D; Madden, PAF; Martin, NG; Maes, HH; Nelson, EC; Peterson, RE; Porjesz, B; Riley, BP; Saccone, N; Stallings, M; Wall, TL; Webb, BT; Wetherill, L; Psychiatric Genomics Consortium Substance Use Disorders Workgroup, ; Edenberg, HJ; Agrawal, A; Gelernter, J (2020). Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.. Mol Psychiatry, 25(8), 1673-1687. [doi]
   (last updated on 2023/06/01)

   Abstract:
   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.