Association of Known Loci With Lipid Levels Among Children and Prediction of Dyslipidemia in Adults

Background— 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. Methods and Results— 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). Conclusions— 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.