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
BACKGROUND AND AIMS: A strong correlation exists between smoking and the use of alcohol and cannabis. This paper uses polygenic risk scores to explore the possibility of overlapping genetic factors. Those scores reflect a combined effect of selected risk alleles for smoking. METHODS: Summary-level P-values were available for smoking initiation, age at onset of smoking, cigarettes per day and smoking cessation from the Tobacco and Genetics Consortium (n between 22,000 and 70,000 subjects). Using different P-value thresholds (0.1, 0.2 and 0.5) from the meta-analysis, sets of 'risk alleles' were defined and used to generate a polygenic risk score (weighted sum of the alleles) for each subject in an independent target sample from the Netherlands Twin Register (n = 1583). The association between polygenic smoking scores and alcohol/cannabis use was investigated with regression analysis. RESULTS: The polygenic scores for 'cigarettes per day' were associated significantly with the number of glasses alcohol per week (P = 0.005, R2 = 0.4-0.5%) and cannabis initiation (P = 0.004, R2 = 0.6-0.9%). The polygenic scores for 'age at onset of smoking' were associated significantly with 'age at regular drinking' (P = 0.001, R2 = 1.1-1.5%), while the scores for 'smoking initiation' and 'smoking cessation' did not significantly predict alcohol or cannabis use. CONCLUSIONS: Smoking, alcohol and cannabis use are influenced by aggregated genetic risk factors shared between these substances. The many common genetic variants each have a very small individual effect size.
Polygenic risk score of age at smoking initiation (with different p-value thresholds) predicting age at regular drinking in target sample from NTR. On vertical axis the standardized regression coefficients (beta) from the regression analyses. In bottom row the explained variance (R2). Bars marked with a *: p<.05
Polygenic risk score of cigarettes per day (with different p-value thresholds) predicting daily drinking in target sample from NTR. On vertical axis the odds ratio’s from the regression analyses. In bottom row the explained variance (R2). Bars marked with a *: p<.05
Polygenic risk score of cigarettes per day (with different p-value thresholds) predicting cannabis initiation in target sample from NTR. On vertical axis the odds ratio’s from the regression analyses. In bottom row the explained variance (R2). Bars marked with a *: p<.05
| 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 |
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