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KMID : 1132720120100020099
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Genomics & Informatics
2012 Volume.10 No. 2 p.99 ~ p.105
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Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population
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Go Min-Jin
Hwang Joo-Yeon
Kim Dong-Joon
Lee Hye-Ja
Jang Han-Byul
Park Kyung-Hee
Song Ji-Hyun
Lee Jong-Young
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Abstract
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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.
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KEYWORD
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childhood obesity, dyslipidemias, genetic risk score, genome-wide association study
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