TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood.

paper Cited Public

Authors: Ducci, Francesca; Kaakinen, Marika; Pouta, Anneli; Hartikainen, Anna-Liisa; Veijola, Juha; Isohanni, Matti; Charoen, Pimphen; Coin, Lachlan; Hoggart, Clive; Ekelund, Jesper; Peltonen, Leena; Freimer, Nelson; Elliott, Paul; Schumann, Gunter; Järvelin, Marjo-Riitta
Year: 2011
Journal: Biological psychiatry
PMID: 21168125
DOI: 10.1016/j.biopsych.2010.09.055
PMCID: PMC3058144

BACKGROUND: CHRNA5-CHRNA3-CHRNB4 and TTC12-ANKK1-DRD2 gene-clusters influence smoking behavior. Our aim was to test developmental changes in their effects as well as the interplays between them and with nongenetic factors. METHODS: Participants included 4762 subjects from a general population-based, prospective Northern Finland 1966 Birth Cohort (NFBC 1966). Smoking behavior was collected at age 14 and 31 years. Information on maternal smoking, socioeconomic status, and novelty seeking were also collected. Structural equation modeling was used to construct an integrative etiologic model including genetic and nongenetic factors. RESULTS: Several single nucleotide polymorphisms in both gene-clusters were significantly associated with smoking. The most significant were in CHRNA3 (rs1051730, p = 1.1 × 10(-5)) and in TTC12 (rs10502172, p = 9.1 × 10(-6)). CHRNA3-rs1051730[A] was more common among heavy/regular smokers than nonsmokers with similar effect-sizes at age 14 years (odds ratio [95% CI]: 1.27 [1.06-1.52]) and 31 years (1.28 [1.13-1.44]). TTC12-rs10502172[G] was more common among smokers than nonsmokers with stronger association at 14 years (1.33 [1.11-1.60]) than 31 years (1.14 [1.02-1.28]). In adolescence, carriers of three-four risk alleles at either CHRNA3-rs1051730 or TTC12-rs10502172 had almost threefold odds of smoking regularly than subjects with no risk alleles. TTC12-rs10502172 effect on smoking in adulthood was mediated by its effect on smoking in adolescence and via novelty seeking. Effect of CHRNA3-rs1051730 on smoking in adulthood was direct. CONCLUSIONS: TTC12-ANKK1-DRD2s seemed to influence smoking behavior mainly in adolescence, and its effect is partially mediated by personality characteristics promoting drug-seeking behavior. In contrast, CHRNA5-CHRNA3-CHRNB4 is involved in the transition toward heavy smoking in mid-adulthood and in smoking persistence. Factors related to familial and social disadvantages were strong independent predictors of smoking.

#	Section	Preview
20	METHODS — Statistical analyses	The combined effect of TTC12-rs10502172 and CHRNA3-rs1051730 on smoking was tested under a…
21	METHODS — Statistical analyses	Linear regression was used to test the two SNPs’ effects on novelty seeking.
22	METHODS — Statistical analyses	In all the above-described analyses covariates entered in the regression models included: sex,…
23	METHODS — Statistical analyses	Haplotype-structures of the two regions were computed with Haploviewv3(50) and haplotype-association…
24	METHODS — Statistical analyses	At age 31 years, the inclusion among non-smokers of participants who were not current-smokers but…
25	METHODS — Statistical analyses	Structural equation modeling (SEM) was used to construct an integrative model including both genetic…
26	METHODS — Statistical analyses	cumulative normal probability distribution. The standardized beta coefficients are used to compare…
27	RESULTS	Several SNPs in both chromosome regions were significantly associated with smoking (Figure-1, Tables…
28	RESULTS	For CHRNA5-CHRNA3-CHRNB4, the most significant SNP was rs1051730 (P=1.1×10−5) mapping in CHRNA3…
29	RESULTS	For TTC12-ANKK1-DRD2, the most significantly associated SNP was rs10502172 (P=9.1×10−6) mapping…
30	RESULTS	Patterns of association observed at age 14 were similar to patterns observed at 31 and very…
31	RESULTS	Of note, the most significant associations survived Bonferroni correction (Bonferroni-corrected…
32	RESULTS — Haplotype analysis	For chromosome 15q25 we identified two haplotype-blocks (Figure S2 in Supplement 1). Significant…
33	RESULTS — Haplotype analysis	For chromosomes 11q23 we identified three haplotype-blocks (Figure S3 in Supplement 1). Significant…
34	RESULTS — Haplotype analysis	None of the haplotypes tested displayed a stronger association signal as compared to rs1051730[A]…
35	RESULTS — Combined effect of TTC12-rs10502172 and CHRNA3-rs1051730	Applying a multiplicative model, we found no significant interaction between TTC12-rs10502172 and…
36	RESULTS — Impact of TTC12-rs10502172 and CHRNA3-rs1051730 on change/persistence of smoking habits	Carriers of TTC12-rs10502172[G] had 1.64 increased odds (95%CI: 1.10–2.45) of being ex-smokers…
37	RESULTS — Impact of maternal smoking	Offspring of mothers who were smoking 1–10 cigarettes/day in pregnancy were at increased risk of…
38	RESULTS — Impact of maternal smoking	Offspring of mothers smoking heavily during pregnancy more likely carried CHRNA3-rs1051730[A] than…
39	RESULTS — Impact of maternal smoking	No significant multiplicative interactive effects were found between maternal smoking and genotype…

Name	Type
15q25 locus	variant
AAGGGAAAAGGGACGGGA local	variant
adolescents	cohort
adulthood	cohort
age 31 local	cohort
alcohol dependence	phenotype
ANKK1	gene
Broad Institute Biological Sample Repository local	cohort
Chrna3	gene
CHRNA3 rs1051730 local	variant
CHRNA3 rs1051730 A local	variant
CHRNA5	gene
CHRNA5-CHRNA3-CHRNB4 cluster	gene
Chrnb4	gene
cigarettes	phenotype
cohort members	cohort
Community-ascertained sample local	cohort
current-smokers local	phenotype
decreased response to nicotine agonists in vitro local	phenotype
DRD2	gene
eagerness to participate local	phenotype
early initiation	phenotype
ever smoking	phenotype
Family socio-economic status local	phenotype
farmers local	phenotype
GGGGAGGGAGAGGAGGGG local	variant
haplotype-block 1 local	variant
haplotype-block 2 local	variant
heavy drinking	phenotype
heavy maternal smoking local	phenotype
heavy/regular-smoker local	phenotype
heavy/regular smoking local	phenotype
heavy-smoker local	phenotype
heavy-smokers local	phenotype
Heavy-smokers local	phenotype
Heavy-smokers at age 31 local	phenotype
heavy smoking	phenotype
heavy-smoking local	phenotype
Heavy smoking at age 31 local	phenotype
heavy use in mid-adulthood local	phenotype
high novelty seeking local	phenotype
High novelty seeking local	phenotype
high-quantity smokers local	phenotype
Illumina Infinium 370cnvDuo array local	drug
inability to quit smoking in pregnancy local	phenotype
late onset-smoker local	phenotype
light maternal smoking local	phenotype
light/non-smoker local	phenotype
Light+non-smokers local	phenotype
light/occasional smoking local	phenotype
light-smoker local	phenotype
light-smokers local	phenotype
Light-smokers local	phenotype
light-smoking local	phenotype
low-quantity smoker local	phenotype
low-quantity smokers local	phenotype
Low socio-economic status local	phenotype
lung cancer	phenotype
marital status	phenotype
maternal smoking	phenotype
Maternal smoking before pregnancy local	drug
men	cohort
mid-adulthood local	cohort
Mothers of participants local	cohort
never smokers	phenotype
nicotine	drug
nicotine addiction	phenotype
nicotine agonists local	drug
nicotine dependence	phenotype
nicotine response local	phenotype
nicotine use	phenotype
non-participants local	cohort
non-smokers	phenotype
Northern Finland 1966 Birth Cohort local	cohort
novelty seeking	phenotype
number of cigarettes smoked per day	phenotype
Occasional smoker local	phenotype
occasional smokers	phenotype
Occasional-smokers at age 14 local	phenotype
occasional smoking at 14 local	phenotype
offspring	cohort
offspring of heavy smoking mothers local	cohort
offspring of light smoking mothers local	cohort
offspring of non-smoking mothers local	cohort
Offspring smoking	phenotype
opioid dependence	phenotype
Other drug dependencies local	phenotype
Parental attitudes local	phenotype
participants	cohort
past smokers local	phenotype
Peer influences	phenotype
persistent-smoker local	phenotype
pleasurable response to smoking	phenotype
professionals local	phenotype
Psychosocial factors	phenotype
Regular-smokers at age 14 local	phenotype
regular smoking	phenotype
Regular smoking at age 14 local	phenotype
rs10502172	variant
rs1051730	variant
rs1076563 local	variant
rs16969968	variant
rs2303380 local	variant
rs2734849 local	variant
sex	phenotype
sex hormones	drug
skilled-workers local	phenotype
smoking	phenotype
smoking at 14 local	phenotype
Smoking at 14 years local	phenotype
smoking at 31 local	phenotype
Smoking at 31 years local	phenotype
smoking at age 14 local	phenotype
Smoking at age 14 local	phenotype
smoking behavior	phenotype
smoking behaviour	phenotype
smoking behaviours local	phenotype
smoking in adolescence local	phenotype
smoking in adulthood local	phenotype
smoking initiation	phenotype
smoking occasionally local	phenotype
smoking persistence	phenotype
smoking quantity	phenotype
smoking regularly local	phenotype
smoking severity	phenotype
SNP	cohort
social disadvantage	phenotype
socio-economic status	phenotype
Taq1A (rs1800497) local	variant
tobacco-related diseases local	phenotype
tobacco use	phenotype
TTC12	gene
TTC12-ANKK1-DRD2 local	gene
TTC12 rs10502172 local	variant
TTC12 rs10502172 G local	variant
Unmarried	phenotype
unmarried mothers local	phenotype
Unmarried status during pregnancy local	phenotype
unskilled-worker families local	phenotype
unskilled-workers local	phenotype
vascular disease	phenotype
women	cohort
young cohorts local	cohort

Citation	PMID	DOI	Status
Amos, CI et al., Nat Genet, 2008, Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1	18385676	10.1038/ng.109	Cited
Barrett, JC et al., Bioinformatics, 2005, Haploview: analysis and visualization of LD and haplotype maps	15297300	10.1093/bioinformatics/bth457	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
Bierut, LJ et al., Am J Med Genet, 2000, Family-based study of the association of the dopamine D2 receptor gene (DRD2) with habitual smoking	10710227	10.1002/(sici)1096-8628(20000214)90:4<299::aid-ajmg7>3.0.co;2-y	Primary
Bierut, LJ et al., Am J Psychiatry, 2008, Variants in nicotinic receptors and risk for nicotine dependence	18519524	10.1176/appi.ajp.2008.07111711	Primary
Bierut, LJ et al., Hum Mol Genet, 2007, Novel genes identified in a high-density genome wide association study for nicotine dependence	17158188	10.1093/hmg/ddl441	Cited
Breslau, N et al., Drug Alcohol Depend, 1993, Early smoking initiation and nicotine dependence in a cohort of young adults	8261877	10.1016/0376-8716(93)90054-t	Cited
Browne, MWCR, Testing structural equation models, 1993, Alternative ways of assessing model fit	—	—	—
Buka, SL et al., Am J Psychiatry, 2003, Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study	14594744	10.1176/appi.ajp.160.11.1978	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
Chen, X et al., Am J Med Genet B Neuropsychiatr Genet, 2009, Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence	19132693	10.1002/ajmg.b.30919	Cited
Cloninger, CR et al., Arch Gen Psychiatry, 1993, A psychobiological model of temperament and character	8250684	10.1001/archpsyc.1993.01820240059008	Cited
Comings, DE et al., Pharmacogenetics, 1996, The dopamine D2 receptor (DRD2) gene: a genetic risk factor in smoking	8845863	10.1097/00008571-199602000-00006	Cited
Ducci, F et al., Addiction, 2008, Genetic approaches to addiction: genes and alcohol	18422824	10.1111/j.1360-0443.2008.02203.x	Cited
Ducci, F et al., Alcohol, 2007, Increased anxiety and other similarities in temperament of alcoholics with and without antisocial personality disorder across three diverse populations	17452294	10.1016/j.alcohol.2007.02.005	Cited
Ducci, F et al., Am J Psychiatry, 2009, Association of substance use disorders with childhood trauma but not African genetic heritage in an African American cohort	19605534	10.1176/appi.ajp.2009.08071068	Cited
Erblich, J et al., Pharmacogenomics J, 2004, Stress-induced cigarette craving: effects of the DRD2 TaqI RFLP and SLC6A3 VNTR polymorphisms	14732864	10.1038/sj.tpj.6500227	Cited
Freathy, RM et al., Hum Mol Genet, 2009, A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy	19429911	10.1093/hmg/ddp216	Cited
Gelernter, J et al., Biol Psychiatry, 2007, Genomewide linkage scan for nicotine dependence: identification of a chromosome 5 risk locus	17081504	10.1016/j.biopsych.2006.08.023	Cited
Gelernter, J et al., Hum Mol Genet, 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
Goldman, D et al., Nat Rev Genet, 2005, The genetics of addictions: uncovering the genes	15995696	10.1038/nrg1635	Cited
Grant, BF, J Subst Abuse, 1998, Age at smoking onset and its association with alcohol consumption and DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey	9720007	10.1016/s0899-3289(99)80141-2	Cited
Hu, LTBP, Structural Equation Modelling: A Multidisciplinary Journal, 1999, Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives	—	—	—
Huang, W et al., Neuropsychopharmacology, 2009, Significant association of ANKK1 and detection of a functional polymorphism with nicotine dependence in an African-American sample	18354387	10.1038/npp.2008.37	Cited
Hung, RJ et al., Nature, 2008, A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25	18385738	10.1038/nature06885	Cited
Isohanni, I et al., Scand J Public Health, 2001, Juvenile and early adulthood smoking and adult educational achievements--a 31-year follow-up of the Northern Finland 1966 Birth Cohort	11484871	10.1177/14034948010290020501	Cited
Isohanni, M et al., Br J Addict, 1991, Determinants of teenage smoking, with special reference to non-standard family background	2054533	10.1111/j.1360-0443.1991.tb03416.x	Cited
Isohanni, M et al., Scand J Soc Med, 1993, The relation between teenage smoking and drinking, with special reference to non-standard family background	8469940	10.1177/140349489302100105	Cited
Isohanni, M et al., Scand J Soc Med, 1995, Smoking or quitting during pregnancy: associations with background and future social factors	7784851	10.1177/140349489502300107	Cited
Johnstone, EC et al., Addict Biol, 2004, The dopamine D2 receptor C32806T polymorphism (DRD2 Taq1A RFLP) exhibits no association with smoking behaviour in a healthy UK population	15511716	10.1080/13556210412331292226	Cited
Kendler, KS et al., Arch Gen Psychiatry, 2008, Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood	18519825	10.1001/archpsyc.65.6.674	Cited
Laucht, M et al., J Am Acad Child Adolesc Psychiatry, 2008, Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence	18434921	10.1097/CHI.0b013e31816bff77	Cited
Liu, JZ et al., Nat Genet, Meta-analysis and imputation refines the association of 15q25 with smoking quantity	20418889	10.1038/ng.572	Cited
Lynch, WJ et al., Psychopharmacology (Berl), 2002, Biological basis of sex differences in drug abuse: preclinical and clinical studies	12404074	10.1007/s00213-002-1183-2	Cited
Makikyro, T et al., Schizophr Res, 1997, Is a child’s risk of early onset schizophrenia increased in the highest social class?	9075303	10.1016/s0920-9964(96)00119-3	Cited
Marshall, L et al., MMWR Surveill Summ, 2006, Youth tobacco surveillance--United States, 2001–2002	16708059	—	Cited
Mitchell, SH, Psychopharmacology (Berl), 1999, Measures of impulsivity in cigarette smokers and non-smokers	10550496	10.1007/pl00005491	Cited
MMWR CDC Surveill Summ, 2000, Youth tobacco surveillance--United States, 1998–1999	11057729	—	Cited
MMWR CDC Surveill Summ, 2001, Youth tobacco surveillance--United States, 2000	11902401	—	Cited
Morley, KI et al., Behav Genet, 2006, A possible smoking susceptibility locus on chromosome 11p12: evidence from sex-limitation linkage analyses in a sample of Australian twin families	16365831	10.1007/s10519-005-9004-0	Cited
Muthén, LMaB, Mplus: statistical analysis with latent variables, 1998	—	—	—
Nat Genet, Genome-wide meta-analyses identify multiple loci associated with smoking behavior	20418890	10.1038/ng.571	Cited
Nelson, DE et al., Am J Public Health, 2008, Long-term trends in adolescent and young adult smoking in the United States: metapatterns and implications	18382001	10.2105/AJPH.2007.115931	Cited
Noble, EP, Alcohol Alcohol Suppl, 1994, Polymorphisms of the D2 dopamine receptor gene and alcoholism and other substance use disorders	8974314	—	Cited
Nyman, ES et al., Am J Med Genet B Neuropsychiatr Genet, 2008, Impact of the dopamine receptor gene family on temperament traits in a population-based birth cohort	19105202	10.1002/ajmg.b.30908	Cited
Rantakallio, P, Paediatr Perinat Epidemiol, 1988, The longitudinal study of the northern Finland birth cohort of 1966	2976931	10.1111/j.1365-3016.1988.tb00180.x	Cited
Rantakallio, P, Scand J Soc Med, 1983, Family background to and personal characteristics underlying teenage smoking. Background to teenage smoking	6612249	10.1177/140349488301100104	Cited
Riala, K et al., J Adolesc Health, 2004, Teenage smoking and substance use as predictors of severe alcohol problems in late adolescence and in young adulthood	15313508	10.1016/j.jadohealth.2003.08.016	Cited
Roth, ME et al., Neurosci Biobehav Rev, 2004, Sex differences in the vulnerability to drug abuse: a review of preclinical studies	15527861	10.1016/j.neubiorev.2004.08.001	Cited
Sabatti, C et al., Nat Genet, 2009, Genome-wide association analysis of metabolic traits in a birth cohort from a founder population	19060910	10.1038/ng.271	Cited
Saccone, NL et al., Am J Med Genet B Neuropsychiatr Genet, 2009, 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, 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
Sherva, R et al., Addiction, 2008, Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking	18783506	10.1111/j.1360-0443.2008.02279.x	Cited
Sovio, U et al., J Health Psychol, 2007, Cloninger’s Temperament dimensions, socio-economic and lifestyle factors and metabolic syndrome markers at age 31 years in the Northern Finland Birth Cohort 1966	17284500	10.1177/1359105307074301	Cited
Stevens, VL et al., Cancer Epidemiol Biomarkers Prev, 2008, Nicotinic receptor gene variants influence susceptibility to heavy smoking	19029397	10.1158/1055-9965.EPI-08-0585	Cited
Thorgeirsson, TE et al., Nature, 2008, A variant associated with nicotine dependence, lung cancer and peripheral arterial disease	18385739	10.1038/nature06846	Cited
Tilloy, E et al., Eur J Cardiovasc Prev Rehabil, Characteristics of current smokers, former smokers, and secondhand exposure and evolution between 1985 and 2007	20489650	10.1097/HJR.0b013e32833a9a0c	Cited
Van De Ven, MO et al., Public Health, Patterns of adolescent smoking and later nicotine dependence in young adults: a 10-year prospective study	20060987	10.1016/j.puhe.2009.11.009	Cited
Volkow, ND et al., J Psychopharmacol, 1999, Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans	10667609	10.1177/026988119901300406	Cited
Wittchen, HU et al., Int J Methods Psychiatr Res, 2008, What are the high risk periods for incident substance use and transitions to abuse and dependence? Implications for early intervention and prevention	18543359	10.1002/mpr.254	Cited
Xu, K et al., Arch Gen Psychiatry, 2004, Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations	15184239	10.1001/archpsyc.61.6.597	Cited

In this knowledge base

Title	Year	PMID
Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.	2016	27166759
Narrative review of genes, environment, and cigarettes.	2016	27124093
Genetic and environmental contributions to the relationships between brain structure and average lifetime cigarette use.	2015	25690561
The Genetics, Neurogenetics and Pharmacogenetics of Addiction.	2014	25045619
ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.	2013	23303482
Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.	2013	24186853
Polygenic risk and the developmental progression to heavy, persistent smoking and nicotine dependence: evidence from a 4-decade longitudinal study.	2013	23536134
The genetic basis of addictive disorders.	2012	22640768
Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking.	2012	22438940
Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence.	2011	21683344

External

Title	Authors	Journal	Year	Link
Genomic approaches to explore susceptibility and pathogenesis of alcohol use disorder and alcohol-associated liver disease.	Norden-Krichmar TM et al.	—	2025	→
Smoking, Genetic Susceptibility and Early Menopause: Unveiling Biological Mechanisms and Potential Therapy Targets.	Liang Y et al.	—	2025	→
Associations between health behaviours, fertility and reproductive outcomes: triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa).	Wootton RE et al.	—	2023	→
Candidate gene-environment interactions in substance abuse: A systematic review.	Jiang Z et al.	—	2023	→
Evaluating the causal effect of tobacco smoking on white matter brain aging: a two-sample Mendelian randomization analysis in UK Biobank.	Mo C et al.	—	2023	→
Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies.	Goldberg LR et al.	—	2022	→
Prenatal Effects of Nicotine on Obesity Risks: A Narrative Review.	White O et al.	—	2022	→
A systems omics-based approach to decode substance use disorders and neuroadaptations.	Veerappa A et al.	—	2021	→
Dynamic change in the association of a cigarettes-per-day polygenic risk score across the numeric range of its corresponding phenotype over adolescence and young adulthood.	Deutsch AR et al.	—	2021	→
Identifying common genome-wide risk genes for major psychiatric traits.	Liu S et al.	—	2020	→
Stability in effects of different smoking-related polygenic risk scores over age and smoking phenotypes.	Deutsch AR et al.	—	2020	→
The IMAGEN study: a decade of imaging genetics in adolescents.	Mascarell Maričić L et al.	—	2020	→
DRD2 and ANKK1 genes associate with late-onset heroin dependence in men.	Tsou CC et al.	—	2019	→
The Finnish psychiatric birth cohort consortium (PSYCOHORTS) - content, plans and perspectives.	Filatova S et al.	—	2019	→
A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response.	Macare C et al.	—	2018	→
GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.	Pasman JA et al.	—	2018	→
The influence of adolescent nicotine exposure on ethanol intake and brain gene expression.	Silva CP et al.	—	2018	→
The Role of Cell Adhesion Molecule Genes Regulating Neuroplasticity in Addiction.	Muskiewicz DE et al.	—	2018	→
Classification Tree Analysis as a Method for Uncovering Relations Between CHRNA5A3B4 and CHRNB3A6 in Predicting Smoking Progression in Adolescent Smokers.	Pugach O et al.	—	2017	→
Genotype × Environment Interaction in Smoking Behaviors: A Systematic Review.	Do EK et al.	—	2017	→
Impulsivity and cue reactivity in smokers with comorbid depression and anxiety: Possible implications for smoking cessation treatment strategies.	Keyser-Marcus L et al.	—	2017	→
Monoamine Oxidase A (<i>MAOA</i>) Gene and Personality Traits from Late Adolescence through Early Adulthood: A Latent Variable Investigation.	Xu MK et al.	—	2017	→
Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.	Yang J et al.	—	2016	→
Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.	Stringer S et al.	—	2016	→
Narrative review of genes, environment, and cigarettes.	Do E et al.	—	2016	→
An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.	Bidwell LC et al.	—	2015	→
Genetic and environmental contributions to the relationships between brain structure and average lifetime cigarette use.	Prom-Wormley E et al.	—	2015	→
NCAM1-TTC12-ANKK1-DRD2 gene cluster and the clinical and genetic heterogeneity of adults with ADHD.	Mota NR et al.	—	2015	→
NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence.	Bidwell LC et al.	—	2015	→
Polygenic score × intervention moderation: an application of discrete-time survival analysis to modeling the timing of first tobacco use among urban youth.	Musci RJ et al.	—	2015	→
The significant association of Taq1A genotypes in DRD2/ANKK1 with smoking cessation in a large-scale meta-analysis of Caucasian populations.	Ma Y et al.	—	2015	→
Updated findings of the association and functional studies of DRD2/ANKK1 variants with addictions.	Ma Y et al.	—	2015	→
Association of the CHRNA4 neuronal nicotinic receptor subunit gene with frequency of binge drinking in young adults.	Coon H et al.	—	2014	→
Commentary on Vink et al. (2014): The polygenic basis of drug use-does context matter?	Lynskey M et al.	—	2014	→
Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults.	Cannon DS et al.	—	2014	→
Genetic variants and early cigarette smoking and nicotine dependence phenotypes in adolescents.	O'Loughlin J 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	→
The Genetics, Neurogenetics and Pharmacogenetics of Addiction.	Demers CH et al.	—	2014	→
ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.	Nelson EC et al.	—	2013	→
Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.	Stephens SH et al.	—	2013	→
Exploring alternate processes contributing to the association between maternal smoking and the smoking behavior among young adult offspring.	Selya AS et al.	—	2013	→
Polygenic risk and the developmental progression to heavy, persistent smoking and nicotine dependence: evidence from a 4-decade longitudinal study.	Belsky DW et al.	—	2013	→
Ventral striatal dopamine synthesis capacity predicts financial extravagance in Parkinson's disease.	Lawrence AD et al.	—	2013	→
A common genetic network underlies substance use disorders and disruptive or externalizing disorders.	Arcos-Burgos M et al.	—	2012	→
ANAPC1 and SLCO3A1 are associated with nicotine dependence: meta-analysis of genome-wide association studies.	Wang KS et al.	—	2012	→
Associations between variation in CHRNA5-CHRNA3-CHRNB4, body mass index and blood pressure in the Northern Finland Birth Cohort 1966.	Kaakinen M et al.	—	2012	→
Connecting ncRNA Cigarette Smoking Studies with Tobacco Use Behaviors and Health Outcomes.	Ehringer MA	—	2012	→
From men to mice: CHRNA5/CHRNA3, smoking behavior and disease.	Ware JJ et al.	—	2012	→
Genetic factors control nicotine self-administration in isogenic adolescent rat strains.	Chen H et al.	—	2012	→
Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.	Tyrrell J et al.	—	2012	→
Glutamate and synaptic plasticity systems and smoking behavior: results from a genetic association study.	dos Santos VA et al.	—	2012	→
Risk factors for adolescent smoking: parental smoking and the mediating role of nicotine dependence.	Selya AS et al.	—	2012	→
The genetic basis of addictive disorders.	Ducci F et al.	—	2012	→
Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking.	Kapoor M et al.	—	2012	→
Developmental perspective on the role of genes in smoking risk.	Gelernter J	—	2011	→
Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence.	Xie P et al.	—	2011	→