Latsuzbaia Ardashel, Jaddoe Vincent W V, Hofman Albert, Franco Oscar H, Felix Janine F
The Generation R Study Group Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
The Generation R Study Group Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Departments of Epidemiology Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
J Lipid Res. 2016 Dec;57(12):2185-2192. doi: 10.1194/jlr.P066902. Epub 2016 Oct 24.
Lipid concentrations are heritable traits. Recently, the number of known genetic loci associated with lipid levels in adults increased from 95 to 157. The effects of these 157 loci have not been tested in children. Considering that lipid levels track from childhood to adulthood, we studied to determine whether these variants already affected lipid concentrations in a large group of 2,645 children with a median age of 6.0 years (95% range 5.7-7.3 years) from the population-based Generation R Study. Twenty-eight SNPs associated with TGs, 39 SNPs associated with total cholesterol (TC), 28 SNPs associated with LDL cholesterol (LDL-C), and 56 SNPs associated with HDL cholesterol (HDL-C) were analyzed individually and combined into genetic risk scores (GRSs). All risk scores were associated with their specific outcomes. The differences in mean absolute lipid and lipoprotein values between the 10% of children with the highest lipid or lipoprotein GRS versus the 10% with the lowest score were 0.28, 0.25, 0.32, and 0.30 mmol/l for TGs, TC, LDL-C, and HDL-C, respectively. In conclusion, we show for the first time that GRSs based on 157 SNPs associated with adult lipid concentrations are associated with lipid levels in children. The genetic background of these phenotypes at least partly overlaps between children and adults.
血脂浓度是可遗传的性状。最近,与成年人血脂水平相关的已知基因位点数量从95个增加到了157个。这些157个位点的影响尚未在儿童中进行测试。鉴于血脂水平从儿童期到成年期具有连续性,我们进行研究以确定这些变异是否已经在来自基于人群的“R代研究”的2645名中位年龄为6.0岁(95%范围5.7 - 7.3岁)的儿童大群体中影响血脂浓度。分别分析了与甘油三酯(TG)相关的28个单核苷酸多态性(SNP)、与总胆固醇(TC)相关的39个SNP、与低密度脂蛋白胆固醇(LDL-C)相关的28个SNP以及与高密度脂蛋白胆固醇(HDL-C)相关的56个SNP,并将它们合并为遗传风险评分(GRS)。所有风险评分均与其特定结果相关。血脂或脂蛋白GRS最高的10%儿童与最低的10%儿童之间,TG、TC、LDL-C和HDL-C的平均绝对血脂和脂蛋白值差异分别为0.28、0.25、0.32和0.30 mmol/l。总之,我们首次表明基于与成人血脂浓度相关的157个SNP的GRS与儿童血脂水平相关。这些表型的遗传背景在儿童和成人之间至少部分重叠。