Interplay of genetic risk factors (CHRNA 5-CHRNA 3-CHRNB4) and cessation treatments in smoking cessation success

Li Shiun Chen, Timothy B. Baker, Megan E. Piper, Naomi Breslau, Dale S. Cannon, Kimberly Doheny, Stephanie M. Gogarten, Eric O. Johnson, Nancy L. Saccone, Jen C. Wang, Robert B. Weiss, Alison M. Goate, Laura Jean Bierut

Research output: Contribution to journalArticle

Abstract

Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking. Method: In a community-based, crosssectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. Results: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success. Conclusions: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.

Original languageEnglish (US)
Pages (from-to)735-742
Number of pages8
JournalAmerican Journal of Psychiatry
Volume169
Issue number7
DOIs
StatePublished - Jul 1 2012

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Withholding Treatment
Smoking Cessation
Haplotypes
Tobacco Use Disorder
Smoking
Drug Therapy
Nicotinic Receptors
Therapeutics
Multigene Family
Proportional Hazards Models
Cross-Sectional Studies
Logistic Models
Placebos
Clinical Trials
Recurrence

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Interplay of genetic risk factors (CHRNA 5-CHRNA 3-CHRNB4) and cessation treatments in smoking cessation success. / Chen, Li Shiun; Baker, Timothy B.; Piper, Megan E.; Breslau, Naomi; Cannon, Dale S.; Doheny, Kimberly; Gogarten, Stephanie M.; Johnson, Eric O.; Saccone, Nancy L.; Wang, Jen C.; Weiss, Robert B.; Goate, Alison M.; Bierut, Laura Jean.

In: American Journal of Psychiatry, Vol. 169, No. 7, 01.07.2012, p. 735-742.

Research output: Contribution to journalArticle

Chen, LS, Baker, TB, Piper, ME, Breslau, N, Cannon, DS, Doheny, K, Gogarten, SM, Johnson, EO, Saccone, NL, Wang, JC, Weiss, RB, Goate, AM & Bierut, LJ 2012, 'Interplay of genetic risk factors (CHRNA 5-CHRNA 3-CHRNB4) and cessation treatments in smoking cessation success', American Journal of Psychiatry, vol. 169, no. 7, pp. 735-742. https://doi.org/10.1176/appi.ajp.2012.11101545
Chen, Li Shiun ; Baker, Timothy B. ; Piper, Megan E. ; Breslau, Naomi ; Cannon, Dale S. ; Doheny, Kimberly ; Gogarten, Stephanie M. ; Johnson, Eric O. ; Saccone, Nancy L. ; Wang, Jen C. ; Weiss, Robert B. ; Goate, Alison M. ; Bierut, Laura Jean. / Interplay of genetic risk factors (CHRNA 5-CHRNA 3-CHRNB4) and cessation treatments in smoking cessation success. In: American Journal of Psychiatry. 2012 ; Vol. 169, No. 7. pp. 735-742.
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abstract = "Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking. Method: In a community-based, crosssectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. Results: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success. Conclusions: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.",
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T1 - Interplay of genetic risk factors (CHRNA 5-CHRNA 3-CHRNB4) and cessation treatments in smoking cessation success

AU - Chen, Li Shiun

AU - Baker, Timothy B.

AU - Piper, Megan E.

AU - Breslau, Naomi

AU - Cannon, Dale S.

AU - Doheny, Kimberly

AU - Gogarten, Stephanie M.

AU - Johnson, Eric O.

AU - Saccone, Nancy L.

AU - Wang, Jen C.

AU - Weiss, Robert B.

AU - Goate, Alison M.

AU - Bierut, Laura Jean

PY - 2012/7/1

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N2 - Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking. Method: In a community-based, crosssectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. Results: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success. Conclusions: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.

AB - Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking. Method: In a community-based, crosssectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. Results: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success. Conclusions: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.

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