Chen Li-Shiun, Hartz Sarah M, Baker Timothy B, Ma Yinjiao, L Saccone Nancy, Bierut Laura J
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
Siteman Cancer Center, Washington University in St Louis, St Louis, MO 63110, USA.
Pharmacogenomics. 2018 Dec;19(18):1383-1394. doi: 10.2217/pgs-2018-0081. Epub 2018 Nov 16.
This study tests whether polygenic risk scores (PRSs) for nicotine metabolism predict smoking behaviors in independent data.
MATERIALS & METHODS: 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.
本研究检验尼古丁代谢的多基因风险评分(PRSs)能否在独立数据中预测吸烟行为。
采用线性回归、逻辑回归和生存分析来分析尼古丁代谢PRSs与尼古丁代谢、吸烟量及戒烟情况。
基于两项全基因组关联研究(GWAS)荟萃分析的尼古丁代谢PRSs显著预测了尼古丁代谢生物标志物(R范围:9.2 - 16%;最小p = 7.6×10)。GWAS最显著的变异体rs56113850显著预测了尼古丁代谢生物标志物(R范围:14 - 17%;最小p = 4.4×10)。没有足够证据表明这些PRSs能预测吸烟量和戒烟情况。
结果表明,基于GWAS荟萃分析的尼古丁代谢PRSs可预测个体的尼古丁代谢,最显著的变异体也有同样作用。我们预计PRSs将进入临床医学,但需要更多研究来开发更全面的基因评分以预测吸烟行为。