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Significant association of CHRNB3 variants with nicotine dependence in multiple ethnic populations

Molecular Psychiatry volume 18, pages 1149–1151 (2013)Cite this article

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Smoking dependence is a complex trait that is significantly influenced by genetics, with an estimated heritability of 0.56. Previous genome-wide association meta-analysis revealed that rs6474412, located about 2.1 kb from the 5′ end of CHRNB3, is significantly associated with the number of cigarettes smoked per day.1 In addition, nominal associations of several variants in or near the CHRNB3 gene with smoking behavior have been reported.2, 3, 4, 5 However, almost all subjects used in these studies were of European ancestry. Given the demonstrated differences across ethnicities with respect to genetics, physiological processes and behavior underlying nicotine dependence (ND),6, 7, 8, 9, 10, 11 it is of great interest to examine whether this gene also is associated with ND in smokers of other ancestries. To attack this issue, we performed a meta-analysis of variants in CHRNB3 in relation to ND by combining data from the studies of subjects of different ethnicities.

Techniques for ascertainment, diagnostic assessments, genotyping, quality control and analysis are detailed elsewhere.12, 13, 14 The four samples included in this study can be described briefly as follows. (1) Mid-South Tobacco Case Control Study (MSTCC): This population consists of 4548 smokers and non-smokers aged 18 years or older of either African American (AA) (N=3161) or European American (EA) (N=1387) origin, who were recruited primarily from the city of Jackson, Mississippi during 2005–2011. Although questionnaires assessing various smoking-related behaviors were administered to each participant, only the Fagerström Test for Nicotine Dependence (FTND) data were analyzed in this study. (2) Study of Addiction: Genetics and Environment (SAGE):12 This study involves three samples: the Collaborative Study on the Genetics of Alcoholism, the Family Study of Cocaine Dependence (FSCD) and the Collaborative Genetic Study of Nicotine Dependence. The FTND score was available for all case subjects; some of them were addicted to cocaine, alcohol, marijuana, opiate and/or other substances as well as tobacco. To minimize the effects of other addictive phenotypes on the association results of CHRNB3 variants with ND, all the phenotypes were included as covariates in our association analysis. For the FSCD sample, only one subject from each family was used. Together, a total of 2428 subjects with EA ancestry and 1136 with AA ancestry were included. (3) A Genome Wide Scan of Lung Cancer and Smoking (CGEMS):13 This study involves two samples. The first contains about 2000 patients with newly diagnosed lung cancer and around 2000 age-, sex- and region-matched controls, all recruited from the Lombardy region of Italy.15 The second sample contains about 850 lung cancer patients and about 850 age- and sex-matched controls.16 Almost all subjects of this study were assessed by a variety of smoking measures, including FTND score, and were of European ancestry. (4) Korea Association Resource (KARE) study:14 All subjects in this study were recruited from two areas, Ansung and Ansan, in South Korea. After appropriate quality control and filtering, 8842 individual samples (4183 men and 4659 women) were eligible. Because no FTND score was available for these smokers, the ND phenotype was analyzed as an ordinal trait with five categories (1–5), as we did previously on this sample17, 18 according to the number of cigarettes smoked per day: non-smoking, <10 cigarettes/day, 11–20 cigarettes/day, 21–30 cigarettes/day, and>31 cigarettes/day, respectively. All studies were conducted under the appropriate ethical approvals, and all subjects provided written informed consent.

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References

  1. Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F et al Nat Genet 2010; 42: 448–453.

    Article  CAS  Google Scholar 

  2. Bierut LJ, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau OF et al Hum Mol Genet 2007; 16: 24–35.

    Article  CAS  Google Scholar 

  3. Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA et al Hum Mol Genet 2007; 16: 36–49.

    Article  CAS  Google Scholar 

  4. Saccone NL, Saccone SF, Hinrichs AL, Stitzel JA, Duan W, Pergadia ML et al Am J Med Genet B Neuropsychiatr Genet 2009; 150B: 453–466.

    Article  CAS  Google Scholar 

  5. Hoft NR, Corley RP, McQueen MB, Schlaepfer IR, Huizinga D, Ehringer MA . Neuropsychopharmacology 2009; 34: 698–706.

    Article  CAS  Google Scholar 

  6. Payne TJ, Diefenbach L . Am J Med Sci 2003; 326: 212–215.

    Article  Google Scholar 

  7. Perez-Stable EJ, Herrera B, Jacob P, Benowitz NL . JAMA 1998; 280: 152–156.

    Article  CAS  Google Scholar 

  8. Fernander AF, Schumacher M, Nasim A . J Black Psychology 2008; 34: 49–69.

    Article  Google Scholar 

  9. Saccone NL, Wang JC, Breslau N, Johnson EO, Hatsukami D, Saccone SF et al Cancer Res 2009; 69: 6848–6856.

    Article  CAS  Google Scholar 

  10. Li MD, Beuten J, Ma JZ, Payne TJ, Lou XY, Garcia V et al Hum Mol Genet 2005; 14: 1211–1219.

    Article  CAS  Google Scholar 

  11. Li MD, Sun D, Lou XY, Beuten J, Payne TJ, Ma JZ . Mol Psychiatry 2007; 12: 462–473.

    Article  CAS  Google Scholar 

  12. Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E et al Proc Natl Acad Sci USA 2010; 107: 5082–5087.

    Article  CAS  Google Scholar 

  13. Landi MT, Chatterjee N, Yu K, Goldin LR, Goldstein AM, Rotunno M et al Am J Hum Genet 2009; 85: 679–691.

    Article  CAS  Google Scholar 

  14. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ et al Nat Genet 2009; 41: 527–534.

    Article  CAS  Google Scholar 

  15. Landi MT, Consonni D, Rotunno M, Bergen AW, Goldstein AM, Lubin JH et al BMC Public Health 2008; 8: 203.

    Article  Google Scholar 

  16. Wang SS, Morton LM, Bergen AW, Lan EZ, Chatterjee N, Kvale P et al Hum Genet 2007; 122: 41–49.

    Article  CAS  Google Scholar 

  17. Yoon D, Kim YJ, Cui WY, Van der Vaart A, Cho YS, Lee JY et al Hum Genet 2012; 131: 1009–1021.

    Article  Google Scholar 

  18. Li MD, Yoon D, Lee JY, Han BG, Niu T, Payne TJ et al PLoS One 2010; 5: e12183.

    Article  Google Scholar 

  19. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR . Genet Epidemiol 2010; 34: 816–834.

    Article  Google Scholar 

  20. Howie BN, Donnelly P, Marchini J . PLoS Genet 2009; 5: e1000529.

    Article  Google Scholar 

  21. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D et al Am J Hum Genet 2007; 81: 559–575.

    Article  CAS  Google Scholar 

  22. Willer CJ, Li Y, Abecasis GR . Bioinformatics 2010; 26: 2190–2191.

    Article  CAS  Google Scholar 

  23. Higgins JP, Thompson SG, Deeks JJ . BMJ 2003; 327: 557–560.

    Article  Google Scholar 

  24. Pe'er I, Yelensky R, Altshuler D, Daly MJ . Genet Epidemiol 2008; 32: 381–385.

    Article  Google Scholar 

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Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    W Y Cui & M D Li

  2. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA

    W Y Cui, S Wang, J Yang, S G Yi & M D Li

  3. Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Korea

    D Yoon, Y-J Kim & T Park

  4. Center for Immunology and Pathology, National Institute of Health, Osong, Korea

    D Yoon

  5. Center for Genome Science, National Institute of Health, Osong, Korea

    Y-J Kim

  6. Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, MS, USA

    T J Payne

  7. Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA

    J Z Ma

  8. Department of Statistics, College of Natural Science, Seoul National University, Seoul, Korea

    T Park

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  1. W Y Cui
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Correspondence to M D Li.

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Cui, W., Wang, S., Yang, J. et al. Significant association of CHRNB3 variants with nicotine dependence in multiple ethnic populations. Mol Psychiatry 18, 1149–1151 (2013). https://doi.org/10.1038/mp.2012.190

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