Genetic regulation of mouse liver metabolite levels
Abstract We profiled and analyzed 283 metabolites representing eight major classes of molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics, Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104 inbred and recombinant inbred strains. We find that me...
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| Format: | Article |
| Language: | English |
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Springer Nature
2014-05-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20135004 |
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| author | Anatole Ghazalpour Brian J Bennett Diana Shih Nam Che Luz Orozco Calvin Pan Raffi Hagopian Aiqing He Paul Kayne Wen‐pin Yang Todd Kirchgessner Aldons J Lusis |
| author_facet | Anatole Ghazalpour Brian J Bennett Diana Shih Nam Che Luz Orozco Calvin Pan Raffi Hagopian Aiqing He Paul Kayne Wen‐pin Yang Todd Kirchgessner Aldons J Lusis |
| author_sort | Anatole Ghazalpour |
| collection | DOAJ |
| description | Abstract We profiled and analyzed 283 metabolites representing eight major classes of molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics, Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104 inbred and recombinant inbred strains. We find that metabolites exhibit a wide range of variation, as has been previously observed with metabolites in blood serum. Using genome‐wide association analysis, we mapped 40% of the quantified metabolites to at least one locus in the genome and for 75% of the loci mapped we identified at least one candidate gene by local expression QTL analysis of the transcripts. Moreover, we validated 2 of 3 of the significant loci examined by adenoviral overexpression of the genes in mice. In our GWAS results, we find that at significant loci the peak markers explained on average between 20 and 40% of variation in the metabolites. Moreover, 39% of loci found to be regulating liver metabolites in mice were also found in human GWAS results for serum metabolites, providing support for similarity in genetic regulation of metabolites between mice and human. We also integrated the metabolomic data with transcriptomic and clinical phenotypic data to evaluate the extent of co‐variation across various biological scales. |
| format | Article |
| id | doaj-art-df721bcfd82e4c309bc0d5074d50bc9d |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2014-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-df721bcfd82e4c309bc0d5074d50bc9d2025-08-20T03:46:34ZengSpringer NatureMolecular Systems Biology1744-42922014-05-0110511310.15252/msb.20135004Genetic regulation of mouse liver metabolite levelsAnatole Ghazalpour0Brian J Bennett1Diana Shih2Nam Che3Luz Orozco4Calvin Pan5Raffi Hagopian6Aiqing He7Paul Kayne8Wen‐pin Yang9Todd Kirchgessner10Aldons J Lusis11Division of Cardiology, Department of Medicine, UCLADivision of Cardiology, Department of Medicine, UCLADivision of Cardiology, Department of Medicine, UCLADivision of Cardiology, Department of Medicine, UCLADepartment of Molecular Cell and Developmental Biology, UCLADepartment of Human Genetics, UCLADivision of Cardiology, Department of Medicine, UCLADepartment of Applied Genomics, Bristol‐Myers SquibbDepartment of Applied Genomics, Bristol‐Myers SquibbDepartment of Applied Genomics, Bristol‐Myers SquibbDepartment of Atherosclerosis Drug Discovery, Bristol‐Myers SquibbDivision of Cardiology, Department of Medicine, UCLAAbstract We profiled and analyzed 283 metabolites representing eight major classes of molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics, Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104 inbred and recombinant inbred strains. We find that metabolites exhibit a wide range of variation, as has been previously observed with metabolites in blood serum. Using genome‐wide association analysis, we mapped 40% of the quantified metabolites to at least one locus in the genome and for 75% of the loci mapped we identified at least one candidate gene by local expression QTL analysis of the transcripts. Moreover, we validated 2 of 3 of the significant loci examined by adenoviral overexpression of the genes in mice. In our GWAS results, we find that at significant loci the peak markers explained on average between 20 and 40% of variation in the metabolites. Moreover, 39% of loci found to be regulating liver metabolites in mice were also found in human GWAS results for serum metabolites, providing support for similarity in genetic regulation of metabolites between mice and human. We also integrated the metabolomic data with transcriptomic and clinical phenotypic data to evaluate the extent of co‐variation across various biological scales.https://doi.org/10.15252/msb.20135004genome‐wide associationlocal eQTLmetabolomeQTLtranscriptome |
| spellingShingle | Anatole Ghazalpour Brian J Bennett Diana Shih Nam Che Luz Orozco Calvin Pan Raffi Hagopian Aiqing He Paul Kayne Wen‐pin Yang Todd Kirchgessner Aldons J Lusis Genetic regulation of mouse liver metabolite levels Molecular Systems Biology genome‐wide association local eQTL metabolome QTL transcriptome |
| title | Genetic regulation of mouse liver metabolite levels |
| title_full | Genetic regulation of mouse liver metabolite levels |
| title_fullStr | Genetic regulation of mouse liver metabolite levels |
| title_full_unstemmed | Genetic regulation of mouse liver metabolite levels |
| title_short | Genetic regulation of mouse liver metabolite levels |
| title_sort | genetic regulation of mouse liver metabolite levels |
| topic | genome‐wide association local eQTL metabolome QTL transcriptome |
| url | https://doi.org/10.15252/msb.20135004 |
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