Emma C Johnson, Dongbing Lai, Jared V Balbona, Alex P Miller, Alexander S Hatoum, Joseph D Deak, Mariela Jennings, David A A Baranger, Marco Galimberti, Kittipong Sanichwankul, Thorgeir Thorgeirsson, Sarah M C Colbert, Keyrun Adhikari, Anna R Docherty, Louisa Degenhardt, Tobias Edwards, Louis Fox, Alexandros Giannelis, Paul W Jeffries, Tellervo Korhonen, Claire L Morrison, Yaira Z Nunez, Teemu Palviainen, Mei-Hsin Su, Pamela N Romero Villela, Leah Wetherill, Emily A Willoughby, Stephanie M Zellers, Laura J Bierut, Jadwiga Buchwald, William E Copeland, Robin P Corley, Naomi P Friedman, Tatiana M Foroud, Nathan A Gillespie, Ian R Gizer, Andrew C Heath, Ian B Hickie, Jaakko Kaprio, Matthew C Keller, James J Lee, Penelope Lind, Pamela A Madden, Hermine H M Maes, Nicholas G Martin, Matt McGue, Sarah E Medland, Elliot C Nelson, John Pearson, Bernice Porjesz, Michael C Stallings, Scott Vrieze, Kirk C Wilhelmson, Henry R Kranzler, Raymond K Walters, Renato Polimanti, Robert Malison, Hang Zhou, Kari Stefansson, Sandra Sanchez-Roige, Marc Potenza, Apiwat Mutirangura, Vorasuk Shotelersuk, Rasmon Kalayasiri, Howard J Edenberg, Joel Gelernter, Arpana Agrawal
{"title":"临床定义的尼古丁依赖的多祖先全基因组关联研究揭示了与其他物质使用障碍和健康相关特征的强遗传相关性。","authors":"Emma C Johnson, Dongbing Lai, Jared V Balbona, Alex P Miller, Alexander S Hatoum, Joseph D Deak, Mariela Jennings, David A A Baranger, Marco Galimberti, Kittipong Sanichwankul, Thorgeir Thorgeirsson, Sarah M C Colbert, Keyrun Adhikari, Anna R Docherty, Louisa Degenhardt, Tobias Edwards, Louis Fox, Alexandros Giannelis, Paul W Jeffries, Tellervo Korhonen, Claire L Morrison, Yaira Z Nunez, Teemu Palviainen, Mei-Hsin Su, Pamela N Romero Villela, Leah Wetherill, Emily A Willoughby, Stephanie M Zellers, Laura J Bierut, Jadwiga Buchwald, William E Copeland, Robin P Corley, Naomi P Friedman, Tatiana M Foroud, Nathan A Gillespie, Ian R Gizer, Andrew C Heath, Ian B Hickie, Jaakko Kaprio, Matthew C Keller, James J Lee, Penelope Lind, Pamela A Madden, Hermine H M Maes, Nicholas G Martin, Matt McGue, Sarah E Medland, Elliot C Nelson, John Pearson, Bernice Porjesz, Michael C Stallings, Scott Vrieze, Kirk C Wilhelmson, Henry R Kranzler, Raymond K Walters, Renato Polimanti, Robert Malison, Hang Zhou, Kari Stefansson, Sandra Sanchez-Roige, Marc Potenza, Apiwat Mutirangura, Vorasuk Shotelersuk, Rasmon Kalayasiri, Howard J Edenberg, Joel Gelernter, Arpana Agrawal","doi":"10.1017/S0033291725100883","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>We replicated the well-known association at the <i>CHRNA5</i> locus (lead single-nucleotide polymorphism [SNP]: rs147144681, <i>p</i> = 1.27E-11 in EUR; lead SNP = rs2036527, <i>p</i> = 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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e234"},"PeriodicalIF":5.5000,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360691/pdf/","citationCount":"0","resultStr":"{\"title\":\"Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.\",\"authors\":\"Emma C Johnson, Dongbing Lai, Jared V Balbona, Alex P Miller, Alexander S Hatoum, Joseph D Deak, Mariela Jennings, David A A Baranger, Marco Galimberti, Kittipong Sanichwankul, Thorgeir Thorgeirsson, Sarah M C Colbert, Keyrun Adhikari, Anna R Docherty, Louisa Degenhardt, Tobias Edwards, Louis Fox, Alexandros Giannelis, Paul W Jeffries, Tellervo Korhonen, Claire L Morrison, Yaira Z Nunez, Teemu Palviainen, Mei-Hsin Su, Pamela N Romero Villela, Leah Wetherill, Emily A Willoughby, Stephanie M Zellers, Laura J Bierut, Jadwiga Buchwald, William E Copeland, Robin P Corley, Naomi P Friedman, Tatiana M Foroud, Nathan A Gillespie, Ian R Gizer, Andrew C Heath, Ian B Hickie, Jaakko Kaprio, Matthew C Keller, James J Lee, Penelope Lind, Pamela A Madden, Hermine H M Maes, Nicholas G Martin, Matt McGue, Sarah E Medland, Elliot C Nelson, John Pearson, Bernice Porjesz, Michael C Stallings, Scott Vrieze, Kirk C Wilhelmson, Henry R Kranzler, Raymond K Walters, Renato Polimanti, Robert Malison, Hang Zhou, Kari Stefansson, Sandra Sanchez-Roige, Marc Potenza, Apiwat Mutirangura, Vorasuk Shotelersuk, Rasmon Kalayasiri, Howard J Edenberg, Joel Gelernter, Arpana Agrawal\",\"doi\":\"10.1017/S0033291725100883\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>We replicated the well-known association at the <i>CHRNA5</i> locus (lead single-nucleotide polymorphism [SNP]: rs147144681, <i>p</i> = 1.27E-11 in EUR; lead SNP = rs2036527, <i>p</i> = 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).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":20891,\"journal\":{\"name\":\"Psychological Medicine\",\"volume\":\"55 \",\"pages\":\"e234\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360691/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychological Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1017/S0033291725100883\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychological Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/S0033291725100883","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.
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.
期刊介绍：
Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
