Igl, Wilmar and Johansson, Asa and Wilson, James F. and Wild, Sarah H. and Polasek, Ozren and Hayward, Caroline and Vitart, Veronique and Hastie, Nicholas and Rudan, Pavao and Gnewuch, Carsten and Schmitz, Gerd and Meitinger, Thomas and Pramstaller, Peter P. and Hicks, Andrew A. and Oostra, Ben A. and van Duijn, Cornelia M. and Rudan, Igor and Wright, Alan and Campbell, Harry and Gyllensten, Ulf (2010) Modeling of Environmental Effects in Genome-Wide Association Studies Identifies SLC2A2 and HP as Novel Loci Influencing Serum Cholesterol Levels. PLOS GENETICS, 6 (1): e1000798. ISSN 1553-7390,
Full text not available from this repository. (Request a copy)Abstract
Genome-wide association studies (GWAS) have identified 38 larger genetic regions affecting classical blood lipid levels without adjusting for important environmental influences. We modeled diet and physical activity in a GWAS in order to identify novel loci affecting total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. The Swedish (SE) EUROSPAN cohort (N(SE) = 656) was screened for candidate genes and the non-Swedish (NS) EUROSPAN cohorts (N(NS) = 3,282) were used for replication. In total, 3 SNPs were associated in the Swedish sample and were replicated in the non-Swedish cohorts. While SNP rs1532624 was a replication of the previously published association between CETP and HDL cholesterol, the other two were novel findings. For the latter SNPs, the p-value for association was substantially improved by inclusion of environmental covariates: SNP rs5400 (p(SE,unadjusted) = 3.6x10(-5), p(SE,adjusted) = 2.26x10(-6), p(NS,unadjusted) = 0.047) in the SLC2A2 ( Glucose transporter type 2) and rs2000999 (p(SE,unadjusted) = 1.1x10(-3), p(SE,adjusted) = 3.8x10(-4), p(NS,unadjusted) = 0.035) in the HP gene (Haptoglobin-related protein precursor). Both showed evidence of association with total cholesterol. These results demonstrate that inclusion of important environmental factors in the analysis model can reveal new genetic susceptibility loci.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FANCONI-BICKEL-SYNDROME; CARDIOVASCULAR-DISEASE; COMMON VARIANTS; POPULATION; COHORT; GENE; LINKAGE; CROATIA; TRAITS; GLUT2; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Aug 2020 08:27 |
| Last Modified: | 24 Aug 2020 08:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25606 |
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