Use of polygenic risk scores of nicotine metabolism in predicting smoking behaviors

• Published in: Pharmacogenomics 2018-12, Vol.19 (18), p.1383-1394
• Main Authors: Chen, Li-Shiun, Hartz, Sarah M, Baker, Timothy B, Ma, Yinjiao, L Saccone, Nancy, Bierut, Laura J
• Format: Article
• Language: English
• Subjects: Adult; Atherosclerosis; Behavior; Biomarkers; Biomarkers - metabolism; Cancer therapies; Chromosomes; Cigarette smoking; Consortia; Cytochrome; Drug addiction; Drug therapy; Female; Genetics; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genotype & phenotype; Humans; Male; Metabolism; Metabolites; Middle Aged; Multifactorial Inheritance - genetics; Nicotine; Nicotine - metabolism; polygenic risk scores; Psychiatry; Risk; Smoking - genetics; Smoking cessation; Smoking Cessation - methods; Studies; Tobacco; Tobacco Use Disorder - genetics
• ISSN: 1462-2416; 1744-8042; 1744-8042
• DOI: 10.2217/pgs-2018-0081

This study tests whether polygenic risk scores (PRSs) for nicotine metabolism predict smoking behaviors in independent data. Linear regression, logistic regression and survival analyses were used to analyze nicotine metabolism PRSs and nicotine metabolism, smoking quantity and smoking cessation. Nicotine metabolism PRSs based on two genome wide association studies (GWAS) meta-analyses significantly predicted nicotine metabolism biomarkers (R range: 9.2-16%; minimum p = 7.6 × 10 ). The GWAS top hit variant rs56113850 significantly predicted nicotine metabolism biomarkers (R range: 14-17%; minimum p = 4.4 × 10 ). There was insufficient evidence for these PRSs predicting smoking quantity and smoking cessation. Results suggest that nicotine metabolism PRSs based on GWAS meta-analyses predict an individual's nicotine metabolism, so does use of the top hit variant. We anticipate that PRSs will enter clinical medicine, but additional research is needed to develop a more comprehensive genetic score to predict smoking behaviors.