TY - JOUR
T1 - Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits
AU - Johnson, Emma C.
AU - Lai, Dongbing
AU - Balbona, Jared V.
AU - Miller, Alex P.
AU - Hatoum, Alexander S.
AU - Deak, Joseph D.
AU - Jennings, Mariela
AU - Baranger, David A.A.
AU - Galimberti, Marco
AU - Sanichwankul, Kittipong
AU - Thorgeirsson, Thorgeir
AU - Colbert, Sarah M.C.
AU - Adhikari, Keyrun
AU - Docherty, Anna R.
AU - Degenhardt, Louisa
AU - Edwards, Tobias
AU - Fox, Louis
AU - Giannelis, Alexandros
AU - Jeffries, Paul W.
AU - Korhonen, Tellervo
AU - Morrison, Claire L.
AU - Nunez, Yaira Z.
AU - Palviainen, Teemu
AU - Su, Mei Hsin
AU - Romero Villela, Pamela N.
AU - Wetherill, Leah
AU - Willoughby, Emily A.
AU - Zellers, Stephanie M.
AU - Bierut, Laura J.
AU - Buchwald, Jadwiga
AU - Copeland, William E.
AU - Corley, Robin P.
AU - Friedman, Naomi P.
AU - Foroud, Tatiana M.
AU - Gillespie, Nathan A.
AU - Gizer, Ian R.
AU - Heath, Andrew C.
AU - Hickie, Ian B.
AU - Kaprio, Jaakko
AU - Keller, Matthew C.
AU - Lee, James J.
AU - Lind, Penelope
AU - Madden, Pamela A.
AU - Maes, Hermine H.M.
AU - Martin, Nicholas G.
AU - McGue, Matt
AU - Medland, Sarah E.
AU - Nelson, Elliot C.
AU - Pearson, John
AU - Porjesz, Bernice
AU - Stallings, Michael C.
AU - Vrieze, Scott
AU - Wilhelmson, Kirk C.
AU - Kranzler, Henry R.
AU - Walters, Raymond K.
AU - Polimanti, Renato
AU - Malison, Robert
AU - Zhou, Hang
AU - Stefansson, Kari
AU - Sanchez-Roige, Sandra
AU - Potenza, Marc
AU - Mutirangura, Apiwat
AU - Shotelersuk, Vorasuk
AU - Kalayasiri, Rasmon
AU - Edenberg, Howard J.
AU - Gelernter, Joel
AU - Agrawal, Arpana
N1 - Publisher Copyright:
© The Author(s), 2025.
PY - 2025/8/20
Y1 - 2025/8/20
N2 - Background. Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. Methods. We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes. Results. We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E-11 in EUR; 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 criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a "problematic tobacco use"factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs). Conclusions. Our results suggest 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.
AB - Background. Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. Methods. We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes. Results. We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E-11 in EUR; 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 criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a "problematic tobacco use"factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs). Conclusions. Our results suggest 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.
KW - addiction
KW - genome-wide association study
KW - nicotine dependence
KW - polygenic risk
KW - psychiatric disorders
UR - https://www.scopus.com/pages/publications/105013552891
UR - https://www.scopus.com/inward/citedby.url?scp=105013552891&partnerID=8YFLogxK
U2 - 10.1017/S0033291725100883
DO - 10.1017/S0033291725100883
M3 - Article
C2 - 40831304
AN - SCOPUS:105013552891
SN - 0033-2917
VL - 55
JO - Psychological medicine
JF - Psychological medicine
M1 - e234
ER -
