Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels.
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 cholester...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC2792712?pdf=render |
| _version_ | 1811276199866925056 |
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| author | Wilmar Igl Asa Johansson James F Wilson Sarah H Wild Ozren Polasek Caroline Hayward Veronique Vitart Nicholas Hastie Pavao Rudan Carsten Gnewuch Gerd Schmitz Thomas Meitinger Peter P Pramstaller Andrew A Hicks Ben A Oostra Cornelia M van Duijn Igor Rudan Alan Wright Harry Campbell Ulf Gyllensten EUROSPAN Consortium |
| author_facet | Wilmar Igl Asa Johansson James F Wilson Sarah H Wild Ozren Polasek Caroline Hayward Veronique Vitart Nicholas Hastie Pavao Rudan Carsten Gnewuch Gerd Schmitz Thomas Meitinger Peter P Pramstaller Andrew A Hicks Ben A Oostra Cornelia M van Duijn Igor Rudan Alan Wright Harry Campbell Ulf Gyllensten EUROSPAN Consortium |
| author_sort | Wilmar Igl |
| collection | DOAJ |
| description | 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) = 3.6 x 10(-5), p(SE,adjusted) = 2.2 x 10(-6), p(NS,unadjusted) = 0.047) in the SLC2A2 (Glucose transporter type 2) and rs2000999 (p(SE,unadjusted) = 1.1 x 10(-3), p(SE,adjusted) = 3.8 x 10(-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. |
| first_indexed | 2024-04-12T23:52:14Z |
| format | Article |
| id | doaj.art-2c8e3e6d842c430892f9814d0afc6139 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-12T23:52:14Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj.art-2c8e3e6d842c430892f9814d0afc61392022-12-22T03:11:38ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042010-01-0161e100079810.1371/journal.pgen.1000798Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels.Wilmar IglAsa JohanssonJames F WilsonSarah H WildOzren PolasekCaroline HaywardVeronique VitartNicholas HastiePavao RudanCarsten GnewuchGerd SchmitzThomas MeitingerPeter P PramstallerAndrew A HicksBen A OostraCornelia M van DuijnIgor RudanAlan WrightHarry CampbellUlf GyllenstenEUROSPAN ConsortiumGenome-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) = 3.6 x 10(-5), p(SE,adjusted) = 2.2 x 10(-6), p(NS,unadjusted) = 0.047) in the SLC2A2 (Glucose transporter type 2) and rs2000999 (p(SE,unadjusted) = 1.1 x 10(-3), p(SE,adjusted) = 3.8 x 10(-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.http://europepmc.org/articles/PMC2792712?pdf=render |
| spellingShingle | Wilmar Igl Asa Johansson James F Wilson Sarah H Wild Ozren Polasek Caroline Hayward Veronique Vitart Nicholas Hastie Pavao Rudan Carsten Gnewuch Gerd Schmitz Thomas Meitinger Peter P Pramstaller Andrew A Hicks Ben A Oostra Cornelia M van Duijn Igor Rudan Alan Wright Harry Campbell Ulf Gyllensten EUROSPAN Consortium Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. PLoS Genetics |
| title | Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. |
| title_full | Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. |
| title_fullStr | Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. |
| title_full_unstemmed | Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. |
| title_short | Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. |
| title_sort | modeling of environmental effects in genome wide association studies identifies slc2a2 and hp as novel loci influencing serum cholesterol levels |
| url | http://europepmc.org/articles/PMC2792712?pdf=render |
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