title: Association of known loci with lipid levels among children and prediction of dyslipidemia in adults.
abstract: 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.
  
  
  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.
authors: Institute for Molecular Medicine, Finland FIMM, University of Helsinki, Helsinki, Finland.
authors: Emmi
authors: E
authors: Tikkanen
authors: Tarja
authors: T
authors: Tuovinen
authors: Elisabeth
authors: E
authors: Widén
authors: Terho
authors: T
authors: Lehtimäki
authors: Jorma
authors: J
authors: Viikari
authors: Mika
authors: M
authors: Kähönen
authors: Leena
authors: L
authors: Peltonen
authors: Olli T
authors: OT
authors: Raitakari
authors: Samuli
authors: S
authors: Ripatti
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D050171:Dyslipidemias / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: D008055:Lipids