Nuotio Joel, Pitkänen Niina, Magnussen Costan G, Buscot Marie-Jeanne, Venäläinen Mikko S, Elo Laura L, Jokinen Eero, Laitinen Tomi, Taittonen Leena, Hutri-Kähönen Nina, Lyytikäinen Leo-Pekka, Lehtimäki Terho, Viikari Jorma S, Juonala Markus, Raitakari Olli T
Circ Cardiovasc Genet. 2017 Jun;10(3). doi: 10.1161/CIRCGENETICS.116.001604.
Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures.
Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3-18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811; =0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758; <0.01). The overall net reclassification improvement and integrated discrimination improvement were significant for all outcomes.
The inclusion of weighted genetic risk scores to lipid-screening programs in childhood could modestly improve the identification of those at highest risk of dyslipidemia in adulthood.
血脂异常是心血管疾病的一个主要可改变风险因素。我们研究了与儿童期血脂指标相比，增加用于血脂水平的新型单核苷酸多态性是否能增强对成人血脂异常的预测。
纳入了2422名年轻芬兰人心血管风险研究的参与者，他们在儿童期（1980年，年龄3至18岁，以及1986年）参加了2次调查，并在成年期的随访研究中（2001年、2007年和2011年）至少参加了一次。我们研究了纳入基于58个低密度脂蛋白胆固醇单核苷酸多态性、71个高密度脂蛋白胆固醇单核苷酸多态性和40个甘油三酯单核苷酸多态性的血脂特异性加权遗传风险评分，与临床儿童期风险因素相比，是否能改善对成人血脂异常的预测。在对儿童期的年龄、性别、体重指数、身体活动和吸烟情况进行校正后，儿童期血脂水平和加权遗传风险评分与所有血脂指标的成人血脂异常风险增加相关。与仅使用儿童期血脂指标预测低密度脂蛋白胆固醇（受试者工作特征曲线下面积0.806对0.811；P=0.01）和甘油三酯（受试者工作特征曲线下面积0.740对受试者工作特征曲线下面积0.758；P<0.01）的方法相比，基于2项儿童期血脂指标和血脂特异性加权遗传风险评分的风险评估提高了预测成人血脂异常的准确性。所有结局的总体净重新分类改善和综合判别改善均具有显著性。
在儿童期血脂筛查项目中纳入加权遗传风险评分，可能会适度改善对成年期血脂异常风险最高者的识别。
