Polygenic risk scores for smoking: predictors for alcohol and cannabis use?
Article first published online: 18 MAR 2014
© 2014 Society for the Study of Addiction
Volume 109, Issue 7, pages 1141–1151, July 2014
How to Cite
Vink, J. M., Hottenga, J. J., de Geus, E. J. C., Willemsen, G., Neale, M. C., Furberg, H. and Boomsma, D. I. (2014), Polygenic risk scores for smoking: predictors for alcohol and cannabis use?. Addiction, 109: 1141–1151. doi: 10.1111/add.12491
- Issue published online: 6 JUN 2014
- Article first published online: 18 MAR 2014
- Accepted manuscript online: 22 JAN 2014 11:15PM EST
- Manuscript Accepted: 15 JAN 2014
- Manuscript Revised: 9 OCT 2013
- Manuscript Received: 17 JUL 2013
- European Research Council. Grant Numbers: 284167, 230374
- Netherlands Organization for Scientific Research. Grant Numbers: 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 31160008, 911-09-032, 56-464-14192
- Center for Medical Systems Biology (CSMB, NWO Genomics)
- NBIC/BioAssist/RK. Grant Number: 2008.024
- Biobanking and Biomolecular Resources Research Infrastructure. Grant Number: 184.021.007
- VU University's Institute for Health and Care Research (EMGO+)
- Neuroscience Campus Amsterdam (NCA)
- European Science Foundation. Grant Number: EU/QLRT-2001-01254
- European Community's Seventh Framework Program. Grant Number: FP7/2007–2013
- ENGAGE. Grant Number: HEALTH-F4-2007-201413
- Rutgers University Cell and DNA Repository. Grant Number: NIMH U24 MH068457-06
- Avera Institute, Sioux Falls, South Dakota (USA)
- National Institutes of Health. Grant Numbers: R01D0042157-01A, DA-18673, DA-026119
- Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health
- US National Institutes of Mental Health. Grant Numbers: MH081802, 1RC2MH089951-01, 1RC2 MH089995-01
- polygenic risk score;
- substance use
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.
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.
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.
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.