1. Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.
- Author
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Johnson EC, Lai D, Miller AP, Hatoum AS, Deak JD, Balbona JV, Baranger DA, Galimberti M, Sanichwankul K, Thorgeirsson T, Colbert SM, Sanchez-Roige S, Adhikari K, Docherty A, Degenhardt L, Edwards T, Fox L, Giannelis A, Jeffries P, Korhonen T, Morrison C, Nunez YZ, Palviainen T, Su MH, Villela PNR, Wetherill L, Willoughby EA, Zellers S, Bierut L, Buchwald J, Copeland W, Corley R, Friedman NP, Foroud TM, Gillespie NA, Gizer IR, Heath AC, Hickie IB, Kaprio JA, Keller MC, Lee JL, Lind PA, Madden PA, Maes HH, Martin NG, McGue M, Medland SE, Nelson EC, Pearson JV, Porjesz B, Stallings M, Vrieze S, Wilhelmsen KC, Walters RK, Polimanti R, Malison RT, Zhou H, Stefansson K, Potenza MN, Mutirangura A, Shotelersuk V, Kalayasiri R, Edenberg HJ, Gelernter J, and Agrawal A
- Abstract
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry, 10,231 of African ancestry, 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes. We replicated the well-known association at the CHRNA5 locus (lead SNP: rs147144681, p =1.27E-11 in European ancestry; lead SNP = rs2036527, p = 6.49e-13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder and 6 of 11 individual diagnostic criteria, but none of the Fagerström Test for Nicotine Dependence (FTND) items, in the independent NESARC-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than did a "problematic tobacco use" factor (a combination of cigarettes per day and nicotine dependence defined by the FTND). Finally, DSM-NicDep was strongly genetically correlated with a GWAS of tobacco use disorder as defined in electronic health records, suggesting that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder., Competing Interests: Conflicts of Interest J.G. is named as an inventor on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. There are no other conflicts of interest to disclose.
- Published
- 2025
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