Polygenic risk scores for smoking: predictors for alcohol and cannabis use?. (18th March 2014)

• Record Type: Journal Article
• Authors: Vink, Jacqueline M.; Hottenga, Jouke Jan; de Geus, Eco J. C.; Willemsen, Gonneke; Neale, Michael C.; Furberg, Helena; Boomsma, Dorret I.
• Is Part Of: Addiction. Volume 109:Number 7(2014:Jul.)
• Page Start: 1141
• Page End: 1151
• Publication Date: 2014-03-18
• Subjects: Alcoholism -- Periodicals; Drug addiction -- Periodicals; 616.86
• DOI: 10.1111/add.12491
• Languages: English
• ISSNs: 0965-2140

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="add12491-sec-0001" sec-type="section"> <title>Background and Aims</title> <p>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.</p> </sec> <sec id="add12491-sec-0002" sec-type="section"> <title>Methods</title> <p>Summary‐level <italic>P</italic>‐values were available for smoking initiation, age at onset of smoking, cigarettes per day and smoking cessation from the Tobacco and Genetics Consortium (<italic>n</italic> between 22 000 and 70 000 subjects). Using different <italic>P</italic>‐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 (<italic>n</italic> = 1583). The association between polygenic smoking scores and alcohol/cannabis use was investigated with regression analysis.</p> </sec> <sec id="add12491-sec-0003" sec-type="section"> <title>Results</title> <p>The polygenic scores for 'cigarettes per day' were associated significantly with the number of glasses alcohol per week (<italic>P</italic> = 0.005, <italic>R</italic><sup>2</sup> = 0.4–0.5%) and cannabis initiation (<italic>P</italic> = 0.004, <italic>R</italic><sup>2</sup> = 0.6–0.9%). The polygenic scores for 'age at onset of smoking' were associated significantly with 'age at regular drinking' (<italic>P</italic> = 0.001, <italic>R</italic><sup>2</sup> = 1.1–1.5%), while the scores for 'smoking initiation' and 'smoking cessation' did not significantly predict alcohol or cannabis use.</p> </sec> <sec id="add12491-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>