Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.

paper Cited Public

Authors: Bergen, Andrew W; Javitz, Harold S; Krasnow, Ruth; Nishita, Denise; Michel, Martha; Conti, David V; Liu, Jinghua; Lee, Won; Edlund, Christopher K; Hall, Sharon; Kwok, Pui-Yan; Benowitz, Neal L; Baker, Timothy B; Tyndale, Rachel F; Lerman, Caryn; Swan, Gary E
Year: 2013
Journal: Pharmacogenetics and genomics
PMID: 23249876
DOI: 10.1097/FPC.0b013e32835cdabd
PMCID: PMC3563676

Figure 1

Effects of rs588765 and rs1051730 on abstinence at end of treatment (EOT) and six months (6MO) by pharmacotherapy group (PG) [nicotine replacement therapy (NRT), bupropion (BUP), placebo (PLA), varenicline (VAR), NRT and BUP (NRT+BUP), chronic NRT and BUP (cNRT+BUP) and chronic BUP and NRT (cBUP+NRT)].

Figure 2

Mediation of rs1051730 association with 6MO abstinence by nicotine dependence measures Fagerstrom Test for Nicotine Dependence (FTND) and cigarettes per day (CPD). a) Association of rs1051730 with 6MO abstinence without adjustment for nicotine dependence measures. The total path from rs1051730 to 6MO abstinence (not including the nicotine dependence measures FTND and CPD) is statistically significant at P<0.05. b) Mediation analyses of rs1051730 with 6MO abstinence with nicotine dependence measures. The direct path has a larger effect size and is more significant (P<0.01), than the total path in (a) above, due to the negative effects of FNTD and CPD on the total path. The path from rs1051730 through FTND to 6MO abstinence is statistically significant at P<0.05. The path from rs1051730 through CPD to 6MO abstinence is not statistically significant, though the association of rs1051730 with CPD is statistically significant at P<0.001.

Figure 3

Receiver Operating Characteristic (ROC) curves for a. placebo (PLA), b. nicotine replacement therapy (NRT) and c. all pharmacotherapy groups (All PG) models at 6MOs. ROC curves are shown for models including demographic variables (demos), demographic variables and rs1051730 (demos_SNP), demographic and dependence variables (demos_dep), demographics and dependence variables and rs1051730 (demos_dep_SNP), and all variables with other chr15q25.1 SNPs, rs588765 and rs578776 (demos_dep_SNP_covSNPs).

#	Section	Preview
20	Results and Discussion — Mediation analysis	We performed post-hoc multivariate mediation analyses to evaluate the association of rs1051730 with…
21	Results and Discussion — Mediation analysis	FTND and CPD included in the mediation model is 2.73 (1.34–5.53) 0.005, and the pseudo-r2 is…
22	Results and Discussion — Receiver Operating Characteristic (ROC) analysis	We performed post-hoc ROC analyses to evaluate the contributions of demographic, dependence, and…
23	Results and Discussion — Receiver Operating Characteristic (ROC) analysis	and rs1051730. For NRT or all PG models, the inclusion of dependence variables, dependence variables…
24	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Chr15q25.1 SNPs	Two chr15q25.1 SNPs (rs588765 and rs1051730) exhibit statistically significant associations with…
25	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Chr15q25.1 SNPs	the minor allele is associated with reduced abstinence in the PLA PG at EOT and at 6MO, and with…
26	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Chr15q25.1 SNPs	dependence on abstinence are related. Mediation analysis examined the relations of rs1051730 with…
27	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Mechanisms	Mechanisms that underlie the two distinct association results involving rs1051730 can be postulated…
28	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Mechanisms	for Axis I disorders [26], rs16969968 (highly correlated with rs1051730 in European ancestry…
29	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Mechanisms	These finding suggest a hypothesis that can be tested in treatment-seeking smokers. Smokers with…
30	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Mechanisms	Conti et al identified the association of rs2072661 with abstinence in analyses of a double-blind…
31	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Limitations	Limitations of our analyses include sample size limitations on statistical power, RCT participant…
32	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Limitations	analysis, namely, pooled regression analysis. Heuristically, all of the studies contributed to the…
33	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Summary	Treatment-seeking smokers with the minor alleles of chr15q25.1 SNPs rs588765 or rs1051730, versus…
34	Results and Discussion — Receiver Operating Characteristic (ROC) analysis — Summary	of rs1051730 with abstinence in individuals randomized to NRT, and to discover, and then to…

Name	Type
1000 Genomes CEU local	cohort
6-month abstinence	phenotype
abstinence	phenotype
abstinence at EOT	phenotype
abstinence outcomes local	phenotype
active pharmacotherapy local	drug
age	phenotype
All PG local	cohort
axis I disorder	phenotype
baseline Fagerström Test for Nicotine Dependence score local	phenotype
Behavioral counseling local	drug
Biospecimen local	drug
buprenorphine	drug
bupropion	drug
chr15q25.1 local	variant
chr15q25.1 nAChR SNP local	variant
chr15q25.1 risk haplotypes local	variant
chr15q25.1 SNPs local	variant
Chrna3	gene
CHRNA5	gene
Chrnb2	gene
Chromosomal sex local	phenotype
cingulate cortex - frontal region circuit local	anatomy
Clinical gender local	phenotype
cognition	phenotype
college degree	phenotype
Combination pharmacotherapy local	drug
comorbidity	phenotype
CPD	phenotype
DNA sample local	drug
dorsal anterior cingulate cortex - ventral striatum circuit local	anatomy
education	phenotype
Eight Randomized Clinical Trials local	cohort
European population	cohort
FTND	phenotype
FTND-associated cingulate circuit local	anatomy
FTND score	phenotype
HapMap	cohort
healthy human smokers local	cohort
individuals with Axis I disorders local	cohort
initial response to tobacco local	phenotype
intra-cingulate cortex circuit local	anatomy
lung cancer	phenotype
marital status	phenotype
medial habenular-interpeduncular nuclear tract local	anatomy
metabolism phenotypes local	phenotype
nAChR local	gene
nAChR SNP local	variant
nAChR SNPs local	variant
nausea	phenotype
nicotine	drug
nicotine dependence	phenotype
nicotine metabolism	phenotype
nicotine patch	drug
nicotine replacement therapy	drug
non-smokers	phenotype
NRT	drug
NRT+BUP local	drug
NRT group local	cohort
NRT PG local	cohort
older smokers local	cohort
Other pharmacotherapies group local	cohort
PG local	cohort
PGs	drug
Pharmacogenetic variation local	variant
pharmacotherapy	drug
Pharmacotherapy arms local	drug
PLA local	cohort
PLA local	drug
placebo group	cohort
placebo patch local	drug
PNAT local	cohort
PNAT Consortium local	cohort
Point prevalence abstinence local	phenotype
quitting success	phenotype
randomization arm local	cohort
randomized controlled trial local	cohort
RCT local	cohort
RCT 3A local	cohort
RCT 3B local	cohort
RCT 5 local	cohort
RCT arms local	cohort
RCTs	cohort
RCTs 3A and 3B local	cohort
relapse	phenotype
Response to tobacco local	phenotype
rs1051730	variant
rs16969968	variant
rs2072661	variant
rs578776	variant
rs588765	variant
seven day point prevalence abstinence local	phenotype
sex	phenotype
short-term abstinence	phenotype
short-term cessation local	phenotype
smoking	phenotype
smoking abstinence	phenotype
smoking cessation	phenotype
smoking heaviness	phenotype
smoking likelihood during pregnancy local	phenotype
smoking phenotypes	phenotype
SNP effects	variant
tobacco use	phenotype
transdermal NRT	drug
treatment response	phenotype
treatment-seeking smokers	cohort
treatment‑seeking smokers local	cohort
United States metropolitan regions local	cohort
varenicline	drug
White	phenotype
white participants	cohort
working memory	phenotype

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In this knowledge base

Title	Year	PMID
Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.	2016	27166759
Smokescreen: a targeted genotyping array for addiction research.	2016	26921259
Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.	2015	26142345
Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers.	2014	24733007
Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6).	2014	24033696
The Genetics, Neurogenetics and Pharmacogenetics of Addiction.	2014	25045619
Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion.	2013	23941313

External

Title	Authors	Journal	Year	Link
Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.	Cinciripini PM et al.	—	2024	→
Nicotine Abuse and Neurodegeneration: Novel Pharmacogenetic Targets to Aid Quitting and Reduce the Risk of Dementia.	Almahasneh F et al.	—	2024	→
A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations.	Prom-Wormley EC et al.	—	2023	→
CHRNA5-A3-B4 and DRD2 Genes and Smoking Cessation Throughout Adulthood: A Longitudinal Study of Women.	Jones SK et al.	—	2023	→
Genetic Associations with Smoking Relapse and Proportion of Follow-up in Smoking Relapse throughout Adulthood in Pre- and Postmenopausal Women.	Jones SK et al.	—	2023	→
Genomic medicine to reduce tobacco and related disorders: Translation to precision prevention and treatment.	Chen LS et al.	—	2023	→
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Identification of Pathogenic Missense Mutations in the CHRNA5 Gene: A Computational Approach.	Kumaraguru M et al.	—	2023	→
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Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women.	Tomaz PRX et al.	—	2018	→
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Pathways to precision medicine in smoking cessation treatments.	Chen LS et al.	—	2018	→
Preparing the Way: Exploiting Genomic Medicine to Stop Smoking.	Bierut LJ et al.	—	2018	→
The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings.	Saccone NL et al.	—	2018	→
Toward the implementation of genomic applications for smoking cessation and smoking-related diseases.	Ramsey AT et al.	—	2018	→
Applying Precision Public Health to Prevent Preterm Birth.	Newnham JP et al.	—	2017	→
Effectiveness of Switching Smoking-Cessation Medications Following Relapse.	Heckman BW et al.	—	2017	→
Hierarchical investigation of genetic influences on response inhibition in healthy young adults.	Weafer J et al.	—	2017	→
Lessons Learned From Past Gene-Environment Interaction Successes.	Ritz BR et al.	—	2017	→
Pharmacogenetic Optimization of Smoking Cessation Treatment.	Chenoweth MJ et al.	—	2017	→
Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation therapies.	Pintarelli G et al.	—	2017	→
Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers.	Schuit E et al.	—	2017	→
Precision medicine and pharmacogenetics: what does oncology have that addiction medicine does not?	Kranzler HR et al.	—	2017	→
Relative contribution of genetic, individual, and self-efficacy factors to smoking cessation in a Chinese rural population.	Wang Q et al.	—	2017	→
Association between variants in nicotinic acetylcholine receptor genes and smoking cessation in a Chinese rural population.	Wang Q et al.	—	2016	→
Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.	Yang J et al.	—	2016	→
Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.	Chen LS et al.	—	2016	→
Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole.	Chan J et al.	—	2016	→
Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use.	Melroy-Greif WE et al.	—	2016	→
Smokescreen: a targeted genotyping array for addiction research.	Baurley JW et al.	—	2016	→
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans.	Jensen KP et al.	—	2015	→
Bacoside A: Role in Cigarette Smoking Induced Changes in Brain.	Vani G et al.	—	2015	→
Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date.	Mamoun M et al.	—	2015	→
CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.	Chen LS et al.	—	2015	→
Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.	Bergen AW et al.	—	2015	→
Effect of the rs1051730-rs16969968 variant and smoking cessation treatment: a meta-analysis.	Leung T et al.	—	2015	→
Gender Considerations in Addiction: Implications for Treatment.	Polak K et al.	—	2015	→
Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.	Chen LS et al.	—	2015	→
Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.	Tyndale RF et al.	—	2015	→
Nicotinic receptors in non-human primates: Analysis of genetic and functional conservation with humans.	Shorey-Kendrick LE et al.	—	2015	→
Pharmacogenetics of nicotine and associated smoking behaviors.	Tanner JA et al.	—	2015	→
The value of control conditions for evaluating pharmacogenetic effects.	Chen LS et al.	—	2015	→
A glimpse into the future - Personalized medicine for smoking cessation.	Bierut LJ et al.	—	2014	→
Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers.	Zhu AZ et al.	—	2014	→
CHRNA5 variant predicts smoking cessation in patients with acute myocardial infarction.	Chen LS et al.	—	2014	→
Commentary: Does mortality from smoking have implications for future Mendelian randomization studies?	Taylor AE et al.	—	2014	→
Genetic influences on smoking and clinical disease. Understanding behavioral and biological pathways with mediation analysis.	Lutz SM et al.	—	2014	→
Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction.	Chen LS et al.	—	2014	→
Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.	Taylor AE et al.	—	2014	→
Nicotine dependence as a moderator of genetic influences on smoking cessation treatment outcome.	Leventhal AM et al.	—	2014	→
Organic cation transporter variation and response to smoking cessation therapies.	Bergen AW et al.	—	2014	→
Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6).	Chen LS et al.	—	2014	→
Re-defininG AddiC(CH3)Tion: genomics and epigenomics on substance use disorders.	Rutter JL et al.	—	2014	→
The Genetics, Neurogenetics and Pharmacogenetics of Addiction.	Demers CH et al.	—	2014	→
Genomics and personalized medicine: <i>CHRNA5-CHRNA3-CHRNB4</i> and smoking cessation treatment.	Chen LS et al.	—	2013	→
Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion.	David SP et al.	—	2013	→
Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density.	Brody AL et al.	—	2013	→