Association of CHRNA4 polymorphisms with smoking behavior in two populations.

paper Cited Public

Authors: Han, Shizhong; Yang, Bao-Zhu; Kranzler, Henry R; Oslin, David; Anton, Raymond; Gelernter, Joel
Year: 2011
Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
PMID: 21445957
DOI: 10.1002/ajmg.b.31177
PMCID: PMC3742073

#	Section	Preview
20	Discussion	The biological link between CHRNA4 and nicotine addiction phenotypes in animal models (Ross et al.,…
21	Discussion	In the first report, Feng et al. (2004) identified two synonymous SNPs in exon 5 (rs1044396,…
22	Discussion	Consistent with this prior work, we detected a significant association of rs2236196 with a…
23	Discussion	In addition, we found that rs1044394, another synonymous SNP in exon 5, was nominally significantly…
24	Discussion	An exploration of the correlation among the three investigated phenotypes could be helpful to…
25	Discussion	Since the ND or FTND cases included in our samples are affected with other substance dependence…
26	Discussion	This study also has limitations. The positive linkage finding by genome scan meta-analysis in our…
27	Discussion	on MAF for the five SNPs. There is a possibility that adjustment for self-reported race in the…
28	Discussion	In summary, our study confirms the previously reported genetic association between CHRNA4…

Name	Type
AA	cohort
African American	cohort
African American female cohort local	cohort
African-Americans	cohort
AIMs	variant
alcohol	phenotype
alcohol dependence	phenotype
animal models	cohort
binary trait	phenotype
candidate SNP	cohort
case cohort	cohort
cases	cohort
causal SNP	cohort
central nervous system	anatomy
CEU	cohort
Chinese male cohort local	cohort
Chrna4	gene
CHRNA4 polymorphisms local	variant
CHRNA4 rare missense variant local	variant
cigarettes	phenotype
cocaine	phenotype
combined cohort	cohort
combined sample	cohort
control	cohort
controls	cohort
CPD	phenotype
DSM-IV diagnosis of Nicotine Dependence local	phenotype
DSM-IV ND local	phenotype
EAs	cohort
European ancestry	cohort
European population	cohort
Fagerström Test for Nicotine Dependence	phenotype
five SNPs local	variant
FTND	phenotype
FTND cases local	phenotype
FTND score	phenotype
full sample	cohort
German cohort	cohort
HapMap	cohort
humans	cohort
maximum number of cigarettes smoked in a 24-hour period local	phenotype
McLean Hospital	cohort
Medical University of South Carolina	cohort
mesolimbic dopamine system	drug
ND cases local	phenotype
never smokers	phenotype
nicotine	drug
nicotine addiction	phenotype
nicotine addiction phenotypes local	phenotype
nicotine dependence	phenotype
Nicotine dependence (ND) local	phenotype
opioid	drug
opioid dependence	phenotype
recruitment site local	cohort
rs1044394	variant
rs1044396	variant
rs1044397	variant
rs12896399 local	variant
rs1426654	variant
rs1540771 local	variant
rs1805007 local	variant
rs2236196	variant
rs2814778	variant
rs3787138	variant
rs6010918 local	variant
self-reported race local	cohort
smoking	phenotype
smoking behavior	phenotype
smoking-related behaviors	phenotype
SNP	cohort
sporadic amyotrophic lateral sclerosis local	phenotype
University of Connecticut Health Center	cohort
University of Pennsylvania	cohort
unrelated controls local	cohort
Yale University School of Medicine	cohort
YRI	cohort

Citation	PMID	DOI	Status
Benowitz, NL, Clin Pharmacol Ther, 2008, Clinical pharmacology of nicotine: implications for understanding, preventing, and treating tobacco addiction	18305452	10.1038/clpt.2008.3	Cited
Bergen, AW et al., Neuropsychopharmacology, 2009, Dopamine genes and nicotine dependence in treatment-seeking and community smokers	19494806	10.1038/npp.2009.52	Cited
Berrettini, W et al., Mol Psychiatry, 2008, Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking	18227835	10.1038/sj.mp.4002154	Cited
Breese, CR et al., J Pharmacol Exp Ther, 1997, Effect of smoking history on [3H]nicotine binding in human postmortem brain	9223534	—	Cited
Breitling, LP et al., Pharmacogenomics J, 2009, Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans	19290018	10.1038/tpj.2009.6	Cited
Buisson, B et al., J Neurosci, 2001, Chronic exposure to nicotine upregulates the human a4b2 nicotinic acetylcholine receptor function	11245666	10.1523/JNEUROSCI.21-06-01819.2001	Cited
Caporaso, N et al., PLoS ONE, 2009, Genome-wide and candidate gene association study of cigarette smoking behaviors	19247474	10.1371/journal.pone.0004653	Cited
Carroll, LS et al., Mol Psychiatry, 2010, Evidence for rare and common genetic risk variants for schizophrenia at protein kinase C, alpha	19786960	10.1038/mp.2009.96	Cited
Conti, DV et al., Hum Mol Genet, 2008, Pharmacogenetics of Nicotine Addiction and Treatment Consortium. Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation	18593715	10.1093/hmg/ddn181	Cited
Diagnostic and Statistical Manual of Mental Disorders, 1994	—	—	—
Ehringer, MA et al., Am J Med Genet (Neuropsychiatr Genet), 2007, Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine	17226798	10.1002/ajmg.b.30464	Cited
Etter, JF et al., Addict Behav, 2009, Association of genes coding for the alpha-4, alpha-5, beta-2 and beta-3 subunits of nicotinic receptors with cigarette smoking and nicotine dependence	19482438	10.1016/j.addbeh.2009.05.010	Cited
Feng, Y et al., Am J Hum Genet, 2004, A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men	15154117	10.1086/422194	Cited
Fenster, CP et al., Ann N Y Acad Sci, 1999, Desensitization of nicotinic receptors in the central nervous system	10414343	10.1111/j.1749-6632.1999.tb11335.x	Cited
Gauderman, WJ, Stat Med, 2002, Sample size requirements for matched case-control studies of gene-environment interaction	11782049	10.1002/sim.973	Cited
Gelernter, J et al., Am J Med Genet (Neuropsychiatr Genet), 2005, Genomewide linkage scan for cocaine dependence and related traits: significant linkages for a cocaine-related trait and cocaine-induced paranoia	15909294	10.1002/ajmg.b.30189	Cited
Gelernter, J et al., Human Molecular Genetics, 2006, Haplotype Spanning TTC12 and ANKK1, Flanked by the DRD2 and NCAM1 Loci, is Strongly Associated to Nicotine Dependence in Two Distinct American Populations	17085484	10.1093/hmg/ddl426	Cited
González, JR et al., Bioinformatics, 2007, SNPassoc: an R package to perform whole genome association studies	17267436	10.1093/bioinformatics/btm025	Cited
Han, S et al., Biol Psychiatry, 2010, Meta-analysis of 15 genome-wide linkage scans of smoking behavior	19819424	10.1016/j.biopsych.2009.08.028	Cited
Heatherton, TF et al., Br J Addict, 1991, The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire	1932883	10.1111/j.1360-0443.1991.tb01879.x	Cited
Hutchison, KE et al., Arch Gen Psychiatry, 2007, CHRNA4 and tobacco dependence: from gene regulation to treatment outcome	17768273	10.1001/archpsyc.64.9.1078	Cited
Knight, HM et al., Am J Hum Genet, 2009, A cytogenetic abnormality and rare coding variants identify ABCA13 as a candidate gene in schizophrenia, bipolar disorder, and depression	19944402	10.1016/j.ajhg.2009.11.003	Cited
Labarca, C et al., Proc Natl Acad Sci USA, 2001, Point mutant mice with hypersensitive a4 nicotinic receptors show dopaminergic deficits and increased anxiety	11226318	10.1073/pnas.041582598	Cited
Li, MD et al., Addiction, 2003, A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins	12492752	10.1046/j.1360-0443.2003.00295.x	Cited
Li, MD et al., Hum Mol Genet, 2005, Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence	15790597	10.1093/hmg/ddi132	Cited
Li, MD, Hum Genet, 2008, Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses	18205015	10.1007/s00439-008-0473-0	Cited
Liu, JZ et al., Nat Genet, 2010, Meta-analysis and imputation refines the association of 15q25 with smoking quantity	20418889	10.1038/ng.572	Cited
Liu, YZ et al., Mol Psychiatry, 2009, genome-wide association analyses suggested a novel mechanism for smoking behavior regulated by IL15	19188921	10.1038/mp.2009.3	Cited
Luna, A et al., Bioinformatics, 2007, snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium plotting package	17234637	10.1093/bioinformatics/btl657	Cited
Nat Genet, 2010, Genome-wide meta-analyses identify multiple loci associated with smoking behavior	20418890	10.1038/ng.571	Cited
Pierucci-Lagha, A et al., Drug Alcohol Depend, 2005, Diagnostic reliability of the Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA)	15896927	10.1016/j.drugalcdep.2005.04.005	Cited
Pritchard, JK et al., Genetics, 2000, Inference of population structure using multilocus genotype data	10835412	10.1093/genetics/155.2.945	Cited
Purcell, S et al., Bioinformatics, 2007, WHAP: haplotype-based association analysis	17118959	10.1093/bioinformatics/btl580	Cited
Ross, SA et al., J Neurosci, 2000, Phenotypic characterization of an a4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse	10964949	10.1523/JNEUROSCI.20-17-06431.2000	Cited
Sabatelli, M et al., Hum Mol Genet, 2009, Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis	19628475	10.1093/hmg/ddp339	Cited
Saccone, NL et al., Am J Med Genet (Neuropsychiatr Genet), Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes	19259974	10.1002/ajmg.b.30828	Cited
Saccone, NL et al., Cancer Res, The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans	19706762	10.1158/0008-5472.CAN-09-0786	Cited
Saccone, SF et al., Hum Mol Genet, 2007, Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs	17135278	10.1093/hmg/ddl438	Cited
Tapper, AR et al., Science, 2004, Nicotine activation of alpha4* receptors: Sufficient for reward, tolerance, and sensitization	15528443	10.1126/science.1099420	Cited
The World Health Report 2002, 2002	—	—	—
Thorgeirsson, TE et al., Nat Genet, 2010, Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior	20418888	10.1038/ng.573	Cited
Thorgeirsson, TE et al., Nature, 2008, A variant associated with nicotine dependence, lung cancer and peripheral arterial disease	18385739	10.1038/nature06846	Cited
Vink, JM et al., Am J Hum Genet, 2009, Genome-wide association study of smoking initiation and current smoking	19268276	10.1016/j.ajhg.2009.02.001	Cited
Weiss, RB et al., PLoS Genet, 2008, A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction	18618000	10.1371/journal.pgen.1000125	Cited
Yang, BZ et al., Genet Epidemiol, 2005, Practical population group assignment with selected informative markers: characteristics and properties of Bayesian clustering via STRUCTURE	15782414	10.1002/gepi.20070	Cited

In this knowledge base

Title	Year	PMID
A regulatory variant of CHRM3 is associated with cannabis-induced hallucinations in European Americans.	2019	31740666
Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.	2013	23249876
Nominal association with CHRNA4 variants and nicotine dependence.	2013	23350800
Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes.	2012	22290489
Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence.	2011	21683344

External

Title	Authors	Journal	Year	Link
Coordination among frequent genetic variants imparts substance use susceptibility and pathogenesis.	Veerappa A et al.	—	2024	→
Hepatocyte CHRNA4 mediates the MASH-promotive effects of immune cell-produced acetylcholine and smoking exposure in mice and humans.	Pan C et al.	—	2023	→
A regulatory variant of CHRM3 is associated with cannabis-induced hallucinations in European Americans.	Cheng Z et al.	—	2019	→
Manifesto for a European research network into Problematic Usage of the Internet.	Fineberg NA et al.	—	2018	→
Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans.	Melroy-Greif WE et al.	—	2017	→
A Genome-wide study of blood pressure in African Americans accounting for gene-smoking interaction.	Taylor JY et al.	—	2016	→
CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation.	Esterlis I et al.	—	2016	→
Heritability of compulsive Internet use in adolescents.	Vink JM et al.	—	2016	→
Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use.	Melroy-Greif WE et al.	—	2016	→
A Genome-Wide Association Study of Emphysema and Airway Quantitative Imaging Phenotypes.	Cho MH et al.	—	2015	→
CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy.	Rocha Santos J et al.	—	2015	→
Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.	Hancock DB et al.	—	2015	→
Nicotinic receptor contributions to smoking: insights from human studies and animal models.	Brunzell DH et al.	—	2015	→
Pharmacogenetics of nicotine and associated smoking behaviors.	Tanner JA et al.	—	2015	→
Rare human nicotinic acetylcholine receptor α4 subunit (CHRNA4) variants affect expression and function of high-affinity nicotinic acetylcholine receptors.	McClure-Begley TD et al.	—	2014	→
Smoking behaviour and compensation: a review of the literature with meta-analysis.	Scherer G et al.	—	2014	→
Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.	Eggert M et al.	—	2013	→
Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.	Bergen AW et al.	—	2013	→
Nominal association with CHRNA4 variants and nicotine dependence.	Kamens HM et al.	—	2013	→
Translational research in nicotine dependence.	Turner JR et al.	—	2013	→
Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes.	Gold AB et al.	—	2012	→
The genetics of addiction-a translational perspective.	Agrawal A et al.	—	2012	→
Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence.	Xie P et al.	—	2011	→