Polygenic Risk Score for Coronary Heart Disease Modifies the Elevated Risk by Cigarette Smoking for Disease Incidence.
Polygenic Risk Score for Coronary Heart Disease Modifies the Elevated Risk by Cigarette Smoking for Disease Incidence.
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DOI：
10.1161/circgen.117.001856
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发表时间：
2018-01
期刊：
影响因子：
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通讯作者：
Orho-Melander M
中科院分区：
文献类型：
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作者：
Hindy G;Wiberg F;Almgren P;Melander O;Orho-Melander M
补充数字内容可在文本中找到。冠心病是一种遗传和环境因素共同作用的多因素疾病。吸烟是冠心病最重要的可改变的危险因素。我们的目的是检验吸烟增加冠心病发病率是否受到冠心病遗传易感性的影响。我们的研究包括来自MDCS（马尔默饮食和癌症研究）的24443名个体。加权多基因风险评分（PRS）是通过对与CHD相关的50个单核苷酸多态性的风险等位基因数量进行求和而产生的。个人被分类为当前，以前或从不吸烟者。主要测试吸烟状况和PRS之间的相互作用，其次与个人单核苷酸多态性。然后，在不同吸烟类别之间测试PRS对CHD发病率的预测作用。在19.4年的中位随访时间内，记录了3217例冠心病事件。吸烟与冠心病的关系被PRS修正（P交互作用=0.005）。吸烟导致的冠心病发病率增加的幅度在PRS最低三分位数的个体中最高（比值比，1.42; 95%置信区间，1.29-1.56/吸烟风险类别），而在最高三分位数的个体中最高（比值比，1.20; 95%置信区间，1.11-1.30/吸烟风险类别）。与女性（P交互=0.44）相比，男性（P交互=0.001）的这种交互作用更强。与目前吸烟者相比，PRS在传统危险因素之上提供了更好的净重新分类和区分（P<0.001）。CHD的遗传易感性会通过吸烟改变相关的CHD风险增加。与吸烟者相比，PRS在从不吸烟者中具有更好的预测性。
Supplemental Digital Content is available in the text. Coronary heart disease (CHD) is a multifactorial disease with both genetic and environmental components. Smoking is the most important modifiable risk factor for CHD. Our aim was to test whether the increased CHD incidence by smoking is modified by genetic predisposition to CHD. Our study included 24 443 individuals from the MDCS (Malmö Diet and Cancer Study). A weighted polygenic risk score (PRS) was created by summing the number of risk alleles for 50 single-nucleotide polymorphisms associated with CHD. Individuals were classified as current, former, or never smokers. Interactions were primarily tested between smoking status and PRS and secondarily with individual single-nucleotide polymorphisms. Then, the predictive use of PRS for CHD incidence was tested among different smoking categories. During a median follow-up time of 19.4 years, 3217 incident CHD cases were recorded. The association between smoking and CHD was modified by the PRS (Pinteraction=0.005). The magnitude of increased incidence of CHD by smoking was highest among individuals in the lowest tertile of PRS (odds ratio, 1.42; 95% confidence interval, 1.29–1.56 per smoking risk category) compared with the highest tertile (odds ratio, 1.20; 95% confidence interval, 1.11–1.30 per smoking risk category). This interaction was stronger among men (Pinteraction=0.001) compared with women (Pinteraction=0.44). The PRS provided a significantly better net reclassification and discrimination on top of traditional risk factors among never smokers compared with current smokers (P<0.001). Genetic predisposition to CHD modifies the associated increased CHD risk by smoking. The PRS has a better predictive use among never smokers compared with smokers.