Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population.
- Author:
Min Jin GO
1
;
Joo Yeon HWANG
;
Dong Joon KIM
;
Hye Ja LEE
;
Han Byul JANG
;
Kyung Hee PARK
;
Jihyun SONG
;
Jong Young LEE
Author Information
- Publication Type:Original Article
- Keywords: childhood obesity; dyslipidemias; genetic risk score; genome-wide association study
- MeSH: Adult; Alleles; Cardiovascular Diseases; Cholesterol; Dyslipidemias; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lipoproteins; Obesity; Polymorphism, Single Nucleotide; Risk Assessment
- From:Genomics & Informatics 2012;10(2):99-105
- CountryRepublic of Korea
- Language:English
- 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.
