Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline.
Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline.
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戒烟药物副作用的基因预测：瓦尼克兰异常梦的全基因组研究。
DOI：
10.1002/cpt.3210
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发表时间：
2024
影响因子：
6.7
通讯作者：
Tyndale,RachelF
中科院分区：
文献类型：
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作者：
Chenoweth,MeghanJ;Kim,YongJae;Nollen,NikkiL;HawkJr,LarryW;Mahoney,MartinC;Lerman,Caryn;Knight,Jo;Tyndale,RachelF
最有效的戒烟单一疗法伐尼克兰（Varenicline）会产生不正常的梦。虽然基因对伐尼克兰相关的恶心和戒烟的影响已被确定，但基因在异常梦中的作用尚不清楚。我们对188名接受varenicline （NCT01314001）治疗的欧洲血统吸烟者进行了异常梦的全基因组关联研究（GWAS）。加性遗传模型检验了伐尼克兰开始服用后2周出现异常梦的可能性。对于顶端基因座，我们测试了对伐尼克兰的选择性、对戒烟的影响、复制和对非洲血统（AA）个体的普遍性。与异常梦相关的最高GWAS变异为rs901886，定位于19号染色体上的icam5内含子2。rs901886 CC、CT和TT基因型的异常梦发生率分别为15%、36%和62% （T对C的优势比为2.94,95%可信区间为1.92 ~ 4.55，P= 2.03e−7；T等位基因频率为52%）。这种rs901886相关性对伐尼克兰具有选择性（尼古丁贴片组和安慰剂组的p值为0.05）。rs901886 T（相对于C等位基因，P= 0.03）和异常梦（P= 0.06）也与伐尼克兰辅助戒烟呈正相关。rs901886 （P= 0.40）和异常梦（P= 0.24）均与依从性无关。在第二次伐尼克兰试验（NCT01836276）中也观察到rs901886对异常梦的类似作用。在AA个体（n= 137）中，rs901886与异常梦无关（P= 0.41），但与位于~ 74.4 kb 5 ' ofICAM5的变异相关（P= 2.56e−3）。icam5基因的变异可能影响异常梦境和伐尼克兰的停药。这些发现为基因优化戒烟方法提供了额外的支持。
Varenicline, the most efficacious smoking cessation monotherapy, produces abnormal dreams. Although genetic contributions to varenicline‐associated nausea and cessation have been identified, the role of genetics in abnormal dreams is unknown. We conducted a genomewide association study (GWAS) of abnormal dreams in 188 European ancestry smokers treated with varenicline (NCT01314001). Additive genetic models examined the likelihood of experiencing abnormal dreams 2 weeks following varenicline initiation. For the top locus, we tested for selectivity to varenicline, effects on cessation, replication, and generalizability to African ancestry (AA) individuals. The top GWAS variant associated with abnormal dreams was rs901886, mapping to intron 2 ofICAM5on chromosome 19. The prevalence of abnormal dreams in those with rs901886 CC, CT, and TT genotypes was 15%, 36%, and 62%, respectively (odds ratio = 2.94 for T vs. C, 95% confidence interval = 1.92–4.55,P= 2.03e−7; T allele frequency = 52%). This rs901886 association was selective to varenicline (Pvalues > 0.05 on nicotine patch and placebo). There were also positive associations for rs901886 T (vs. C allele,P= 0.03) and for abnormal dreams (P= 0.06) with varenicline‐aided cessation. Neither rs901886 (P= 0.40) nor abnormal dreams (P= 0.24) were associated with adherence. A similar direction of effect of rs901886 on abnormal dreams was observed in a second varenicline trial (NCT01836276). In AA individuals (n= 137), rs901886 was not associated with abnormal dreams (P= 0.41), but there was an association for a variant located ~ 74.4 kb 5′ ofICAM5(P= 2.56e−3). Variation inICAM5may influence abnormal dreams and cessation on varenicline. These findings provide additional support for genetically optimized smoking cessation approaches.