Tikkanen Emmi, Tuovinen Tarja, Widén Elisabeth, Lehtimäki Terho, Viikari Jorma, Kähönen Mika, Peltonen Leena, Raitakari Olli T, Ripatti Samuli
Institute for Molecular Medicine, Finland FIMM, University of Helsinki, Helsinki, Finland.
Circ Cardiovasc Genet. 2011 Dec;4(6):673-80. doi: 10.1161/CIRCGENETICS.111.960369. Epub 2011 Oct 7.
Recent genome-wide association studies have found 95 distinct genetic loci associated with high-density (HDL-C) and low-density (LDL-C) lipoprotein cholesterol, total cholesterol (TC), and triglycerides (TG), using adult samples. It is not known if these variants are associated with lipid levels in children and adolescents and if the genetic risk score (GRS), based on these variants, could improve adulthood dyslipidemia prediction over the childhood lipid measurements.
We used 2443 participants of the Cardiovascular Risk in Young Finns study cohort with up to 5 measurements of serum lipids taken between ages 3 and 45 years to estimate the effect of individual single-nucleotide polymorphisms and the GRS on lipids. The GRSs were strongly associated with lipids in all age groups (1.5 × 10(-20)<P<8.7 × 10(-12) for HDL-C, 3.5 × 10(-27)<P<5.6 × 10(-09) for LDL-C, 2.0 × 10(-25)<P<5.2 × 10(-09) for TC, and 4.1 × 10(-20)<P<8.4 × 10(-05) for TG). Jointly, the lipid loci explained 11.8-26.7% of the total variance in lipids among 3- to 6-year-old children, and the proportion dropped over age, except for TG. The discrimination of adult hypertriglyceridemia improved when GRS was added to childhood lipid measurement (C statistic=0.04, P=0.01).
Previously identified lipid loci are associated with lipid levels in children and adolescents and explain up to more than 2 times of the lipid variation in children compared with adults. The TG-GRS improves the risk discrimination over childhood lipid measurement for adult hypertriglyceridemia.
近期全基因组关联研究利用成人样本发现了95个与高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）和甘油三酯（TG）相关的不同基因位点。尚不清楚这些变异是否与儿童和青少年的血脂水平相关，以及基于这些变异的遗传风险评分（GRS）能否比儿童期血脂测量更好地预测成年期血脂异常。
我们使用了年轻芬兰人心血管风险研究队列中的2443名参与者，他们在3至45岁之间进行了多达5次血脂测量，以评估个体单核苷酸多态性和GRS对血脂的影响。GRS与所有年龄组的血脂均密切相关（HDL-C的P值为1.5×10⁻²⁰<P<8.7×10⁻¹²，LDL-C的P值为3.5×10⁻²⁷<P<5.6×10⁻⁰⁹，TC的P值为2.0×10⁻²⁵<P<5.2×10⁻⁰⁹，TG的P值为4.1×10⁻²⁰<P<8.4×10⁻⁰⁵）。总体而言，这些血脂基因位点解释了3至6岁儿童血脂总变异的11.8%至26.7%，除TG外，该比例随年龄增长而下降。将GRS添加到儿童期血脂测量中可改善对成人高甘油三酯血症的鉴别能力（C统计量=0.04，P=0.01）。
先前确定的血脂基因位点与儿童和青少年的血脂水平相关，与成人相比，其解释的儿童血脂变异是成人的两倍多。TG-GRS比儿童期血脂测量能更好地鉴别成人高甘油三酯血症的风险。
