Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking

Manav Kapoor, Jen Chyong Wang, Sarah Bertelsen, Kathy Bucholz, John P. Budde, Anthony Hinrichs, Arpana Agrawal, Andrew Brooks, David Chorlian, Danielle Dick, Victor Hesselbrock, Tatiana Foroud, John Kramer, Samuel Kuperman, Niklas Manz, John Nurnberger, Bernice Porjesz, John Rice, Jay Tischfield, Xiaoling XueiMarc Schuckit, Howard Edenberg, Laura J. Bierut, Alison M. Goate

Research output: Contribution to journalArticle

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Abstract

Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28<r 2<0.56) with variants that have previously been reported to affect risk for nicotine dependence and smoking related diseases in adults. The data suggests that an age-associated relationship underlies the association of SNPs in CHRNB4 with onset of chronic smoking behaviors in adolescents and young adults and may improve genetic information that will lead to better prevention and intervention for substance use disorders among adolescents and young adults.

Original languageEnglish
Article numbere33513
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 16 2012

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alcohol abuse
Chromosomes
young adults
Age of Onset
Genes
nicotine
Smoking
chromosomes
multigene family
Alcoholism
Young Adult
Tobacco Use Disorder
Nicotine
cigarettes
lung neoplasms
Multigene Family
linkage disequilibrium
quantitative traits
respiratory tract diseases
multivariate analysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kapoor, M., Wang, J. C., Bertelsen, S., Bucholz, K., Budde, J. P., Hinrichs, A., ... Goate, A. M. (2012). Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking. PLoS One, 7(3), [e33513]. https://doi.org/10.1371/journal.pone.0033513

Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking. / Kapoor, Manav; Wang, Jen Chyong; Bertelsen, Sarah; Bucholz, Kathy; Budde, John P.; Hinrichs, Anthony; Agrawal, Arpana; Brooks, Andrew; Chorlian, David; Dick, Danielle; Hesselbrock, Victor; Foroud, Tatiana; Kramer, John; Kuperman, Samuel; Manz, Niklas; Nurnberger, John; Porjesz, Bernice; Rice, John; Tischfield, Jay; Xuei, Xiaoling; Schuckit, Marc; Edenberg, Howard; Bierut, Laura J.; Goate, Alison M.

In: PLoS One, Vol. 7, No. 3, e33513, 16.03.2012.

Research output: Contribution to journalArticle

Kapoor, M, Wang, JC, Bertelsen, S, Bucholz, K, Budde, JP, Hinrichs, A, Agrawal, A, Brooks, A, Chorlian, D, Dick, D, Hesselbrock, V, Foroud, T, Kramer, J, Kuperman, S, Manz, N, Nurnberger, J, Porjesz, B, Rice, J, Tischfield, J, Xuei, X, Schuckit, M, Edenberg, H, Bierut, LJ & Goate, AM 2012, 'Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking', PLoS One, vol. 7, no. 3, e33513. https://doi.org/10.1371/journal.pone.0033513
Kapoor, Manav ; Wang, Jen Chyong ; Bertelsen, Sarah ; Bucholz, Kathy ; Budde, John P. ; Hinrichs, Anthony ; Agrawal, Arpana ; Brooks, Andrew ; Chorlian, David ; Dick, Danielle ; Hesselbrock, Victor ; Foroud, Tatiana ; Kramer, John ; Kuperman, Samuel ; Manz, Niklas ; Nurnberger, John ; Porjesz, Bernice ; Rice, John ; Tischfield, Jay ; Xuei, Xiaoling ; Schuckit, Marc ; Edenberg, Howard ; Bierut, Laura J. ; Goate, Alison M. / Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking. In: PLoS One. 2012 ; Vol. 7, No. 3.
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abstract = "Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.282<0.56) with variants that have previously been reported to affect risk for nicotine dependence and smoking related diseases in adults. The data suggests that an age-associated relationship underlies the association of SNPs in CHRNB4 with onset of chronic smoking behaviors in adolescents and young adults and may improve genetic information that will lead to better prevention and intervention for substance use disorders among adolescents and young adults.",
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AU - Kapoor, Manav

AU - Wang, Jen Chyong

AU - Bertelsen, Sarah

AU - Bucholz, Kathy

AU - Budde, John P.

AU - Hinrichs, Anthony

AU - Agrawal, Arpana

AU - Brooks, Andrew

AU - Chorlian, David

AU - Dick, Danielle

AU - Hesselbrock, Victor

AU - Foroud, Tatiana

AU - Kramer, John

AU - Kuperman, Samuel

AU - Manz, Niklas

AU - Nurnberger, John

AU - Porjesz, Bernice

AU - Rice, John

AU - Tischfield, Jay

AU - Xuei, Xiaoling

AU - Schuckit, Marc

AU - Edenberg, Howard

AU - Bierut, Laura J.

AU - Goate, Alison M.

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