Genetic contribution to lipid levels in early life based on 158 loci validated in adults: The FAMILY study

Abstract

The contribution of polymorphisms associated with adult lipids in early life is unknown. We studied 158 adult lipid polymorphisms in 1440 participants (544 children, 544 mothers and 324 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) birth cohort. Total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) measurements were collected at birth, 3 and 5 years of age. Polymorphisms were genotyped using the Illumina Cardio-Metabochip array. Genotype scores (GS) were calculated for TC, HDL-C, LDL-C and TG. Linear and mixed-effects regressions adjusted for sex, age and population stratification were performed. The GS was associated with LDL-C level at 3 and 5 years (β = 0.017±0.003, P = 2.9 × 10'8; β = 0.020±0.003, P = 5.7 × 10'9) and from birth to 5 years (β = 0.013±0.003, P = 2.6 × 10'7). The GS was associated with TC level at 3 and 5 years (β = 0.009±0.002, P = 9.1 × 10'7; β = 0.009±0.002, P = 7.7 × 10'6). CETP rs3764261 was associated with the HDL-C level from birth to 5 years (β = 0.064±0.014, P = 7.4 × 10'6). AMPD3 rs2923084 was associated with the HDL-C level at 5 years (β = 0.096±0.024, P = 9.7 × 10'5). Known loci associated with blood lipids in adults are associated with TC, LDL-C and HDL-C, but not TG in early life. Genetically predisposed children may benefit from early lipid lowering preventative strategies.