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

• Published in: Genomics & informatics Vol. 10; no. 2; pp. 99 - 105
• Main Authors: Go, Min Jin, Hwang, Joo-Yeon, Kim, Dong-Joon, Lee, Hye-Ja, Jang, Han Byul, Park, Kyung-Hee, Song, Jihyun, Lee, Jong-Young
• Format: Journal Article
• Language: English
• Published: Korea (South) Korea Genome Organization 01.06.2012; BioMed Central; 한국유전체학회
• Subjects: childhood obesity; dyslipidemias; genetic risk score; genome-wide association study; 자연과학일반; genetic risk score; dyslipidemias; childhood obesity; genome-wide association study
• ISSN: 1598-866X; 2234-0742; 2234-0742
• DOI: 10.5808/GI.2012.10.2.99

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.