Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population
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...
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BioMed Central
2012-06-01
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| Series: | Genomics & Informatics |
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| Online Access: | http://genominfo.org/upload/pdf/gni-10-99.pdf |
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| author | Min Jin Go Joo-Yeon Hwang Dong-Joon Kim Hye-Ja Lee Han Byul Jang Kyung-Hee Park Jihyun Song Jong-Young Lee |
| author_facet | Min Jin Go Joo-Yeon Hwang Dong-Joon Kim Hye-Ja Lee Han Byul Jang Kyung-Hee Park Jihyun Song Jong-Young Lee |
| author_sort | Min Jin Go |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bd6ec15060eb40a4b21c420a26f92dc1 |
| institution | Kabale University |
| issn | 1598-866X 2234-0742 |
| language | English |
| publishDate | 2012-06-01 |
| publisher | BioMed Central |
| record_format | Article |
| series | Genomics & Informatics |
| spelling | doaj-art-bd6ec15060eb40a4b21c420a26f92dc12025-02-03T02:51:21ZengBioMed CentralGenomics & Informatics1598-866X2234-07422012-06-011029910510.5808/GI.2012.10.2.9939Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean PopulationMin Jin Go0Joo-Yeon Hwang1Dong-Joon Kim2Hye-Ja Lee3Han Byul Jang4Kyung-Hee Park5Jihyun Song6Jong-Young Lee7Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongwon 363-951, Korea.Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongwon 363-951, Korea.Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongwon 363-951, Korea.Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Cheongwon 363-951, Korea.Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Cheongwon 363-951, Korea.Department of Family Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 431-796, Korea.Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Cheongwon 363-951, Korea.Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongwon 363-951, Korea.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.http://genominfo.org/upload/pdf/gni-10-99.pdfchildhood obesitydyslipidemiasgenetic risk scoregenome-wide association study |
| spellingShingle | Min Jin Go Joo-Yeon Hwang Dong-Joon Kim Hye-Ja Lee Han Byul Jang Kyung-Hee Park Jihyun Song Jong-Young Lee Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population Genomics & Informatics childhood obesity dyslipidemias genetic risk score genome-wide association study |
| title | Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population |
| title_full | Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population |
| title_fullStr | Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population |
| title_full_unstemmed | Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population |
| title_short | Effect of Genetic Predisposition on Blood Lipid Traits Using Cumulative Risk Assessment in the Korean Population |
| title_sort | effect of genetic predisposition on blood lipid traits using cumulative risk assessment in the korean population |
| topic | childhood obesity dyslipidemias genetic risk score genome-wide association study |
| url | http://genominfo.org/upload/pdf/gni-10-99.pdf |
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