Genomics Inform.  2012 Jun;10(2):99-105. 10.5808/GI.2012.10.2.99.

Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population

• Go MJ
• Hwang JY
• Kim DJ
• Lee HJ
• Jang HB
• Park KH
• Song J
• Lee JY

• KMID: 2166491
• DOI: http://doi.org/10.5808/GI.2012.10.2.99

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.

Keyword

childhood obesity; dyslipidemias; genetic risk score; genome-wide association study

MeSH Terms

Adult
Alleles
Cardiovascular Diseases
Cholesterol
Dyslipidemias
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Lipoproteins
Obesity
Polymorphism, Single Nucleotide
Risk Assessment
Cholesterol
Lipoproteins