title: Effect of genetic predisposition on blood lipid traits using cumulative risk assessment in the korean population.
abstract: Dyslipidemia, mainly characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, is an important etiological factor in the development of cardiovascular disease (CVD). Considering the relationship between childhood obesity and CVD risk, it would be worthwhile to evaluate whether previously identified lipid-related variants in adult subjects are associated with lipid variations in a childhood obesity study (n = 482). In an association analysis for 16 genome-wide association study (GWAS)-based candidate loci, we confirmed significant associations of a genetic predisposition to lipoprotein concentrations in a childhood obesity study. Having two loci (rs10503669 at LPL and rs16940212 at LIPC) that showed the strongest association with blood levels of TG and HDL-C, we calculated a genetic risk score (GRS), representing the sum of the risk alleles. It has been observed that increasing GRS is significantly associated with decreased HDL-C (effect size, -1.13 ± 0.07) compared to single nucleotide polymorphism combinations without two risk variants. In addition, a positive correlation was observed between allelic dosage score and risk allele (rs10503669 at LPL) on high TG levels (effect size, 10.89 ± 0.84). These two loci yielded consistent associations in our previous meta-analysis. Taken together, our findings demonstrate that the genetic architecture of circulating lipid levels (TG and HDL-C) overlap to a large extent in childhood as well as in adulthood. Post-GWAS functional characterization of these variants is further required to elucidate their pathophysiological roles and biological mechanisms.
authors.affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongwon 363-951, Korea.
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Go
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Dong-Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Hye-Ja
authors.initials: HJ
authors.lastname: Lee
authors.forename: Han Byul
authors.initials: HB
authors.lastname: Jang
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Park
authors.forename: Jihyun
authors.initials: J
authors.lastname: Song
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
keywords: childhood obesity; dyslipidemias; genetic risk score; genome-wide association study