Polygenic risk scores for smoking: predictors for alcohol and cannabis use?

paper Cited Public

Authors: Vink, Jacqueline M; Hottenga, Jouke Jan; de Geus, Eco J C; Willemsen, Gonneke; Neale, Michael C; Furberg, Helena; Boomsma, Dorret I
Year: 2014
Journal: Addiction (Abingdon, England)
PMID: 24450588
DOI: 10.1111/add.12491
PMCID: PMC4048635

#	Section	Preview
0	Introduction	A strong correlation exists between smoking and the use of other substances like alcohol and…
1	Introduction	In the past years, genome-wide association (GWA) studies to smoking behavior revealed several…
2	Introduction	For cannabis use several candidate genes are suggested based on linkage and association studies…
3	Introduction	Rietschel and Treutlein (2013) reviewed the current literature on alcohol GWAS and concluded that…
4	Introduction	Twin-family studies suggested a genetic overlap between use of different substances, but so far none…
5	Introduction	Some examples exist of well-know substance specific genes that are also associated with another…
6	Introduction	The effect sizes of individual risk alleles underlying substance use are small, with most genotype…
7	Introduction	Polygenic risk scores have been used to summarize genetic effects among a group of genetic variants…
8	Introduction	but not to several non-psychiatric diseases (which suggested disease specificity). The polygenic…
9	Introduction	In the present study, polygenic risk scores for smoking were identified based on the large…
10	Methods — Discovery sample from TAG consortium	The TAG consortium reported summary-level p-values of the GWA meta-analyses of 4 smoking phenotypes…
11	Methods — Discovery sample from TAG consortium	Four dimensions of smoking behavior were analyzed (38):
12	Methods — Discovery sample from TAG consortium	Ever versus never regular smokers (Ever): Regular smokers (1) were defined as those who reported…
13	Methods — Discovery sample from TAG consortium	Age at onset of smoking (AOS): Age of smoking initiation was the reported age the participant…
14	Methods — Discovery sample from TAG consortium	Cigarettes per day (CPD): the average or maximum (depending on study) number of cigarettes smoked…
15	Methods — Discovery sample from TAG consortium	Smoking cessation (Former): Smoking cessation contrasted former (=0) versus current (=1) smokers.
16	Methods — Discovery sample from TAG consortium	Each study conducted uniform cross-sectional analyses for each smoking phenotype using an additive…
17	Methods — Discovery sample from TAG consortium	The analyses were run separately for males and females. Since the TAG consortium did not detect…
18	Methods — Target sample from NTR	The target sample consisted of subjects from the Netherlands Twin Register (NTR) who were not part…
19	Methods — Target sample from NTR	Age at regular alcohol use: Answer options: <11 years, 12, 13, 14, 15, 16, 17, 18 years or older,…

Name	Type
15q25 locus	variant
19q13.2 region local	variant
203 subjects local	cohort
ADH	gene
age	phenotype
Age at cannabis initiation local	phenotype
Age at first cannabis local	phenotype
age at first cannabis use	phenotype
age at first cigarette local	phenotype
Age at first cigarette local	phenotype
age at initiation	phenotype
age at smoking initiation	phenotype
age at smoking onset local	phenotype
Age at smoking onset polygenic risk score local	drug
age first cannabis local	phenotype
alcohol	phenotype
Alcohol consumption (glasses per week) local	phenotype
alcohol dependence	phenotype
Alcohol Initiation	phenotype
alcohol preference	phenotype
Alcohol Use	phenotype
ALDH2	gene
bipolar disorder	phenotype
birth cohort	cohort
cannabis dependence	phenotype
cannabis initiation	phenotype
cannabis initiation age >=18 local	phenotype
cannabis use	phenotype
case/control status	phenotype
Chrna3	gene
CHRNA5	gene
Chrnb4	gene
cigarettes	phenotype
Common Genetic Risk Variation local	variant
common variants	cohort
CPD	phenotype
current smoking	phenotype
discovery sample	cohort
DNA variants	cohort
drinks >20 glasses alcohol per week local	phenotype
ENGAGE consortium local	cohort
Ever local	phenotype
ever cannabis use	phenotype
ever regular smokers local	phenotype
ever smoking	phenotype
former smokers	phenotype
GAIN-NTR study local	cohort
general substance-use genes local	gene
heavy persistent smoking local	phenotype
independent target sample local	cohort
Netherlands Twin Register	cohort
never initiated alcohol use local	phenotype
never regular smokers local	phenotype
never started to drink regularly local	phenotype
never tried cannabis local	phenotype
nicotine dependence	phenotype
nicotinic receptor genes local	gene
Nicotinic Receptor Genes local	gene
non-psychiatric diseases local	phenotype
Non-Psychiatric Diseases local	phenotype
NTR	cohort
NTR target sample local	cohort
Number of glasses alcohol per week local	phenotype
Oxford-GlaxoSmithKline local	cohort
polygenic risk score	cohort
polygenic risk score (4 SNPs 15q25.1 + 2 SNPs 19q13.2) local	drug
polygenic risk score (92 SNPs) local	drug
Polygenic risk score for age at onset of smoking local	phenotype
polygenic risk score for age at smoking onset local	drug
polygenic risk score for age at smoking onset local	phenotype
Polygenic risk score for alcohol local	variant
Polygenic risk score for cannabis local	variant
polygenic risk score for CPD local	phenotype
polygenic risk score for CPD local	variant
Polygenic risk score for CPD local	phenotype
Polygenic risk score for ever smoking local	phenotype
Polygenic risk score for former smoking local	phenotype
Polygenic risk score for smoking local	variant
psychiatric disorders	phenotype
regular alcohol use	phenotype
risk allele	cohort
schizophrenia	phenotype
sex	phenotype
smoking	phenotype
smoking behavior	phenotype
smoking cessation	phenotype
smoking initiation	phenotype
smoking persistence	phenotype
smoking phenotypes	phenotype
Smoking polygenic risk score local	drug
Smoking variables local	phenotype
SNP	cohort
started regular drinking after age 17 local	phenotype
substance abuse	phenotype
substance-specific genes local	gene
substance use	phenotype
survey 2 local	cohort
Survey 2 local	cohort
Survey 2–8 local	cohort
survey 3 local	cohort
Survey 3 local	cohort
survey 4 local	cohort
survey 8 local	cohort
Survey 8 local	cohort
TAG consortium	cohort
TAG meta-analyses local	cohort
TAG study local	cohort
Tobacco and Genetics Consortium	cohort
Two Traits local	phenotype
variant	cohort
voluntary ethanol consumption	phenotype

Citation	PMID	DOI	Status
Agrawal, A et al., Addiction Biology, 2011, A genome-wide association study of DSM-IV cannabis dependence	21668797	10.1111/j.1369-1600.2010.00255.x	Primary
Agrawal, A et al., Addiction, 2009, Candidate genes for cannabis use disorders: findings, challenges and directions	19335651	10.1111/j.1360-0443.2009.02504.x	Cited
Agrawal, A et al., Addiction, 2012, The co-occurring use and misuse of cannabis and tobacco: a review	22300456	10.1111/j.1360-0443.2012.03837.x	Cited
Amos, CI et al., Nat Genet, 2010, Chipping away at the genetics of smoking behavior	20428092	10.1038/ng0510-366	Cited
Belsky, DwMTEBTB, JAMA Psychiatry, 2013, Polygenic risk and the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-decade longitudinal study	23536134	10.1001/jamapsychiatry.2013.736	Cited
Bierut, LJ et al., Human Molecular Genetics, 2007, Novel genes identified in a high-density genome wide association study for nicotine dependence	17158188	10.1093/hmg/ddl441	Cited
Boomsma, DI et al., Twin Res Hum Genet, 2006, Netherlands Twin Register: from twins to twin families	17254420	10.1375/183242706779462426	Cited
Broms, U et al., Hum Genet, 2006, Genetic architecture of smoking behavior: a study of Finnish adult twins	16611469	10.1375/183242706776403046	Cited
Davies, G et al., Mol Psychiatry, 2011, Genome-wide association studies establish that human intelligence is highly heritable and polygenic	21826061	10.1038/mp.2011.85	Cited
de Moor, MH et al., Front Genet, 2011, Heritability of problem drinking and the genetic overlap with personality in a general population sample	22303371	10.3389/fgene.2011.00076	Cited
Demirkan, A et al., Mol Psychiatry, 2010, Genetic risk profiles for depression and anxiety in adult and elderly cohorts	20567237	10.1038/mp.2010.65	Cited
Distel, MA et al., Addiction, 2011, Age moderates non-genetic influences on the initiation of cannabis use: a twin-sibling study in Dutch adolescents and young adults	21489006	10.1111/j.1360-0443.2011.03465.x	Cited
Dudbridge, F, PLoS Genet, 2013, Power and Predictive Accuracy of Polygenic Risk Scores	23555274	10.1371/journal.pgen.1003348	Cited
Evans, DM et al., Human Molecular Genetics, 2009, Harnessing the information contained within genome-wide association studies to improve individual prediction of complex disease risk	19553258	10.1093/hmg/ddp295	Cited
Hardie, TL et al., Addictive Behaviors, 2006, Genetic correlations between smoking initiation and smoking behaviors in a twin sample	16675152	10.1016/j.addbeh.2006.02.010	Cited
Heath, AC et al., Twin Research, 2002, Estimating two-stage models for genetic influences on alcohol, tobacco or drug use initiation and dependence vulnerability in twin and family data	11931689	10.1375/1369052022983	Cited
John, U et al., Alcohol and Alcoholism, 2003, Strength of the relationship between tobacco smoking, nicotine dependence and the severity of alcohol dependence syndrome criteria in a population-based sample	14633650	10.1093/alcalc/agg122	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
Kendler, KS et al., Psychological Medicine, 1999, A population-based twin study in women of smoking initiation and nicotine dependence	10218922	10.1017/s0033291798008022	Cited
Koopmans, JR et al., Alcoholism: Clinical and Experimental Research, 1997, Association between alcohol use and smoking in adolescent and young adult twins: a bivariate genetic analysis	9161615	—	Cited
Li, MD et al., Addiction, 2003, A meta-analysis of estimated and environmental effects on smoking behavior in male and female adult twins	12492752	10.1046/j.1360-0443.2003.00295.x	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, QR et al., American Journal of Medical Genetics Part B (Neuropsychiatric Genetics), 2006, Addiction Molecular Genetics: 639,401 SNP whole genome association identifies many “cell adhesion” genes	17099884	10.1002/ajmg.b.30436	Cited
Lubke, GH et al., Biol Psychiatry, 2012, Estimating the genetic variance of major depressive disorder due to all single nucleotide polymorphisms	22520966	10.1016/j.biopsych.2012.03.011	Cited
Luciano, M et al., American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012, Genome-wide association uncovers shared genetic effects among personality traits and mood states	22628180	10.1002/ajmg.b.32072	Cited
Madden, PAF et al., Alcoholism, 2002, Shared genetic vulnerability in alcohol and cigarette use and dependence	12500120	10.1097/01.ALC.0000040960.15151.30	Cited
Madden, PAF et al., Behavior Genetics, 1999, The genetics of smoking persistence in men and women: a multicultural study	10857247	10.1023/a:1021674804714	Cited
Middeldorp, CM et al., Translational Psychiatry, 2011, The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data	22833196	10.1038/tp.2011.45	Primary
Nat Genet, 2010, Genome-wide meta-analyses identify multiple loci associated with smoking behavior	20418890	10.1038/ng.571	Cited
Nature, 2009, Common polygenic variation contributes to risk of schizophrenia and bipolar disorder	19571811	10.1038/nature08185	Cited
Rietschel, M et al., Annals of the New York Academy of Sciences, 2013, The genetics of alcohol dependence	23170934	10.1111/j.1749-6632.2012.06794.x	Cited
Sullivan, PF et al., Nicotine Tobacco Res, 1999, The genetic epidemiology of smoking	11768187	10.1080/14622299050011811	Cited
Symons, M et al., Behavior Genetics, 2010, Delineation of the Role of Nicotinic Acetylcholine Receptor Genes in Alcohol Preference in Mice	20496163	10.1007/s10519-010-9366-9	Cited
The Lancet, 2013, Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis	23453885	10.1016/S0140-6736(12)62129-1	Cited
Thorgeirsson, TE et al., Nat Genet, 2010, Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior	20418888	10.1038/ng.573	Cited
Uhl, GR et al., BMC genetics, 2007, Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs	17407593	10.1186/1471-2156-8-10	Cited
van Beek, JH et al., Behav Genet, 2012, Stable genetic effects on symptoms of alcohol abuse and dependence from adolescence into early adulthood	21818662	10.1007/s10519-011-9488-8	Cited
van Scheltinga, AFT et al., Psychological Medicine, 2013, Schizophrenia genetic variants are not associated with intelligence	23410598	10.1017/S0033291713000196	Cited
Verweij, KJ et al., Addiction, 2010, Genetic and environmental influences on cannabis use initiation and problematic use: a meta-analysis of twin studies	20402985	10.1111/j.1360-0443.2009.02831.x	Cited
Verweij, KJH et al., Addiction Biology, 2012, The genetic aetiology of cannabis use initiation: a meta-analysis of genome-wide association studies and a SNP-based heritability estimation	22823124	10.1111/j.1369-1600.2012.00478.x	Cited
Vink, JM et al., Addict Behav, 2010, Heritability of cannabis initiation in Dutch adult twins	19793625	10.1016/j.addbeh.2009.09.015	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
Vink, JM et al., Behav Genet, 2005, Heritability of smoking initiation and nicotine dependence	15971021	10.1007/s10519-004-1327-8	Cited
Vink, JM et al., Behav Genet, 2006, Genome-wide linkage scan to identify loci for age at first cigarette in Dutch sibling pairs	16374522	10.1007/s10519-005-9012-0	Cited
Vink, JM et al., Pharmacogenomics J, 2004, Linkage analysis of smoking initiation and quantity in Dutch sibling pairs	15170444	10.1038/sj.tpj.6500255	Cited
Visscher, PM et al., Twin Res Hum Genet, 2010, A commentary on ‘common SNPs explain a large proportion of the heritability for human height’ by Yang et al. (2010)	21142928	10.1375/twin.13.6.517	Cited
Vorstman, JAS et al., American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2013, No evidence that common genetic risk variation is shared between schizophrenia and autism	23193033	10.1002/ajmg.b.32121	Cited
Vrieze, S et al., Human genetics, 2012, The interplay of genes and adolescent development in substance use disorders: leveraging findings from GWAS meta-analyses to test developmental hypotheses about nicotine consumption	22492059	10.1007/s00439-012-1167-1	Cited
Willemsen, G et al., Twin Res Hum Genet, 2010, The Netherlands Twin Register Biobank:A Resource for Genetic Epidemiological Studies	20477721	10.1375/twin.13.3.231	Cited
Willemsen, G et al., Twin Research and Human Genetics, 2013, The Adult Netherlands Twin Register: Twenty-Five Years of Survey and Biological Data Collection	23298648	10.1017/thg.2012.140	Cited
Wray, NR et al., Genome Research, 2007, Prediction of individual genetic risk to disease from genome-wide association studies	17785532	10.1101/gr.6665407	Cited
Young, S et al., Behavior Genetics, 2006, Genetic and Environmental Vulnerabilities Underlying Adolescent Substance Use and Problem Use: General or Specific?	16619135	10.1007/s10519-006-9066-7	Cited

In this knowledge base

Title	Year	PMID
Psychosocial moderation of polygenic risk for cannabis involvement: the role of trauma exposure and frequency of religious service attendance.	2019	31636251
The genetic epidemiology of substance use disorder: A review.	2017	28938182
The genetic relationship between cannabis and tobacco cigarette use in European- and African-American female twins and siblings.	2016	27114204
Are genetic variants for tobacco smoking associated with cannabis involvement?	2015	25770649

External

Title	Authors	Journal	Year	Link
Predicting Genetic Risk for Impulsivity and Substance Use in Adolescence	Wade NE et al.	—	2025	—
The Moderating Role of Genetic and Environmental Risk Factors for Schizophrenia on the Relationship between Autistic Traits and Psychosis Expression in the General Population.	Karacam Dogan M et al.	—	2025	→
Associations between polygenic risk scores and accelerated brain ageing in smokers.	Yang Z et al.	—	2023	→
Associations of polygenic risk scores for smoking heaviness and lifetime cannabis use with tobacco and cannabis co-use trajectories among African Americans.	Rabinowitz JA et al.	—	2023	→
Risk for alcohol use problems in severe mental illness: Interactions with sex and racial/ethnic minority status.	Levit JD et al.	—	2023	→
Polygenic Score for Physical Activity Is Associated with Multiple Common Diseases.	Sillanpää E et al.	—	2022	→
Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort.	Liang X et al.	—	2021	→
Genetic overlap and causality between substance use disorder and attention-deficit and hyperactivity disorder.	Vilar-Ribó L et al.	—	2021	→
Genetics of substance use disorders in the era of big data.	Gelernter J et al.	—	2021	→
Multi-Polygenic Analysis of Nicotine Dependence in Individuals of European Ancestry.	Risner VA et al.	—	2021	→
Genome-Wide Association Study of Opioid Cessation.	Cox JW et al.	—	2020	→
Genomic prediction of alcohol-related morbidity and mortality.	Kiiskinen T et al.	—	2020	→
Illicit drug use and the genetic overlap with Cannabis use.	Vink JM et al.	—	2020	→
Redefining phenotypes to advance psychiatric genetics: Implications from hierarchical taxonomy of psychopathology.	Waszczuk MA et al.	—	2020	→
Association between polygenic risk for tobacco or alcohol consumption and liability to licit and illicit substance use in young Australian adults.	Chang LH et al.	—	2019	→
Associations between polygenic risk for tobacco and alcohol use and liability to tobacco and alcohol use, and psychiatric disorders in an independent sample of 13,999 Australian adults.	Chang LH et al.	—	2019	→
Genetics of alcohol use disorder: a review.	Deak JD et al.	—	2019	→
Genetic Vulnerability for Smoking and Cannabis Use: Associations With E-Cigarette and Water Pipe Use.	Allegrini AG et al.	—	2019	→
Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts.	Sanchez-Roige S et al.	—	2019	→
Genome-wide association study of alcohol use disorder identification test (AUDIT) scores in 20 328 research participants of European ancestry.	Sanchez-Roige S et al.	—	2019	→
Psychosocial moderation of polygenic risk for cannabis involvement: the role of trauma exposure and frequency of religious service attendance.	Meyers JL et al.	—	2019	→
Using Classification Trees to Examine Predictors of Marijuana Use Among a Wide Range of Variables.	Wallace GT et al.	—	2019	→
Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two-sample bidirectional Mendelian randomization study.	Verweij KJH et al.	—	2018	→
Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.	Taylor M et al.	—	2018	→
Polygenic risk for alcohol consumption and its association with alcohol-related phenotypes: Do stress and life satisfaction moderate these relationships?	Mies GW et al.	—	2018	→
The genetic and environmental architecture of substance use development from early adolescence into young adulthood: a longitudinal twin study of comorbidity of alcohol, tobacco and illicit drug use.	Waaktaar T et al.	—	2018	→
Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117).	Clarke TK et al.	—	2017	→
Patterns of cannabis use during adolescence and their association with harmful substance use behaviour: findings from a UK birth cohort.	Taylor M et al.	—	2017	→
The genetic epidemiology of substance use disorder: A review.	Prom-Wormley EC et al.	—	2017	→
Tobacco and alcohol use during adolescence: Interactive mechanisms in animal models.	Abreu-Villaça Y et al.	—	2017	→
Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.	Habes M et al.	—	2016	→
Associations between smoking and caffeine consumption in two European cohorts.	Treur JL et al.	—	2016	→
Commentary on Verweij et al. (2016): Conduct problems and substance use-genetic and environmental perspectives on sex differences.	Few LR et al.	—	2016	→
Connecting the dots, genome-wide association studies in substance use.	Nivard MG et al.	—	2016	→
Exploration of a Polygenic Risk Score for Alcohol Consumption: A Longitudinal Analysis from the ALSPAC Cohort.	Taylor M et al.	—	2016	→
Genetic and Environmental Factors Associated with Cannabis Involvement.	Bogdan R et al.	—	2016	→
Genome-Wide Association of Heroin Dependence in Han Chinese.	Kalsi G et al.	—	2016	→
Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures.	Kapoor M et al.	—	2016	→
Molecular genetic approaches to understanding the comorbidity of psychiatric disorders.	Gizer IR	—	2016	→
Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population.	Otto JM et al.	—	2016	→
The genetic relationship between cannabis and tobacco cigarette use in European- and African-American female twins and siblings.	Agrawal A et al.	—	2016	→
Are genetic variants for tobacco smoking associated with cannabis involvement?	Agrawal A et al.	—	2015	→
Cannabis use among Swedish men in adolescence and the risk of adverse life course outcomes: results from a 20 year-follow-up study.	Danielsson AK et al.	—	2015	→
Genetics of alcoholism.	Iyer-Eimerbrink PA et al.	—	2014	→