Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population

  • Go, Min-Jin (Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex) ;
  • Hwang, Joo-Yeon (Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex) ;
  • Kim, Dong-Joon (Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex) ;
  • Lee, Hye-Ja (Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health) ;
  • Jang, Han-Byul (Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health) ;
  • Park, Kyung-Hee (Department of Family Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Song, Ji-Hyun (Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health) ;
  • Lee, Jong-Young (Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex)
  • Received : 2012.04.10
  • Accepted : 2012.05.22
  • Published : 2012.06.30
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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, $-1.13{\pm}0.07$) 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, $10.89{\pm}0.84$). 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.

Keywords

References

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