Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Department of Genetic Counseling, Bay Path University, Longmeadow, MA, USA.
Nicotine Tob Res. 2022 Oct 17;24(10):1573-1580. doi: 10.1093/ntr/ntac043.
Tobacco use disorder is a complex behavior with a strong genetic component. Genome-wide association studies (GWAS) on smoking behaviors allow for the creation of polygenic risk scores (PRSs) to approximate genetic vulnerability. However, the utility of smoking-related PRSs in predicting smoking cessation in clinical trials remains unknown.
We evaluated the association between polygenic risk scores and bioverified smoking abstinence in a meta-analysis of two randomized, placebo-controlled smoking cessation trials. PRSs of smoking behaviors were created using the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) consortium summary statistics. We evaluated the utility of using individual PRS of specific smoking behavior versus a combined genetic risk that combines PRS of all four smoking behaviors. Study participants came from the Transdisciplinary Tobacco Use Research Centers (TTURCs) Study (1091 smokers of European descent), and the Genetically Informed Smoking Cessation Trial (GISC) Study (501 smokers of European descent).
PRS of later age of smoking initiation (OR [95% CI]: 1.20, [1.04-1.37], p = .0097) was significantly associated with bioverified smoking abstinence at end of treatment. In addition, the combined PRS of smoking behaviors also significantly predicted bioverified smoking abstinence (OR [95% CI] 0.71 [0.51-0.99], p = .045).
PRS of later age at smoking initiation may be useful in predicting smoking cessation at the end of treatment. A combined PRS may be a useful predictor for smoking abstinence by capturing the genetic propensity for multiple smoking behaviors.
There is a potential for polygenic risk scores to inform future clinical medicine, and a great need for evidence on whether these scores predict clinically meaningful outcomes. Our meta-analysis provides early evidence for potential utility of using polygenic risk scores to predict smoking cessation amongst smokers undergoing quit attempts, informing further work to optimize the use of polygenic risk scores in clinical care.
吸烟障碍是一种具有强烈遗传成分的复杂行为。对吸烟行为的全基因组关联研究（GWAS）允许创建多基因风险评分（PRS）来近似遗传易感性。然而，吸烟相关PRS 在临床试验中预测戒烟的效用仍然未知。
我们在两项随机、安慰剂对照戒烟临床试验的荟萃分析中评估了多基因风险评分与生物验证的吸烟戒断之间的关联。使用 GWAS 和酒精和尼古丁使用的测序联盟（GSCAN）联盟汇总统计数据创建了吸烟行为的 PRS。我们评估了使用特定吸烟行为的个体 PRS 与合并所有四种吸烟行为的遗传风险的综合遗传风险来预测戒烟的效用。研究参与者来自跨学科烟草使用研究中心（TTURC）研究（1091 名欧洲血统吸烟者）和遗传信息吸烟戒烟试验（GISC）研究（501 名欧洲血统吸烟者）。
吸烟起始年龄较晚的 PRS（OR [95%CI]：1.20，[1.04-1.37]，p =.0097）与治疗结束时的生物验证吸烟戒断显著相关。此外，吸烟行为的综合 PRS 也显著预测了生物验证的吸烟戒断（OR [95%CI] 0.71 [0.51-0.99]，p =.045）。
吸烟起始年龄较晚的 PRS 可能有助于预测治疗结束时的戒烟。综合 PRS 通过捕获多种吸烟行为的遗传倾向，可能是预测吸烟戒断的有用预测因子。
多基因风险评分有可能为未来的临床医学提供信息，并且非常需要有关这些评分是否预测临床有意义的结果的证据。我们的荟萃分析为使用多基因风险评分预测试图戒烟的吸烟者戒烟的潜在效用提供了早期证据，为进一步优化多基因风险评分在临床护理中的使用提供了信息。
