Cis and trans effects of human genomic variants on gene expression.
Gene expression is a heritable cellular phenotype that defines the function of a cell and can lead to diseases in case of misregulation. In order to detect genetic variations affecting gene expression, we performed association analysis of single nucleotide polymorphisms (SNPs) and copy number varian...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004461 |
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| _version_ | 1849331088819748864 |
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| author | Julien Bryois Alfonso Buil David M Evans John P Kemp Stephen B Montgomery Donald F Conrad Karen M Ho Susan Ring Matthew Hurles Panos Deloukas George Davey Smith Emmanouil T Dermitzakis |
| author_facet | Julien Bryois Alfonso Buil David M Evans John P Kemp Stephen B Montgomery Donald F Conrad Karen M Ho Susan Ring Matthew Hurles Panos Deloukas George Davey Smith Emmanouil T Dermitzakis |
| author_sort | Julien Bryois |
| collection | DOAJ |
| description | Gene expression is a heritable cellular phenotype that defines the function of a cell and can lead to diseases in case of misregulation. In order to detect genetic variations affecting gene expression, we performed association analysis of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with gene expression measured in 869 lymphoblastoid cell lines of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in cis and in trans. We discovered that 3,534 genes (false discovery rate (FDR) = 5%) are affected by an expression quantitative trait locus (eQTL) in cis and 48 genes are affected in trans. We observed that CNVs are more likely to be eQTLs than SNPs. In addition, we found that variants associated to complex traits and diseases are enriched for trans-eQTLs and that trans-eQTLs are enriched for cis-eQTLs. As a variant affecting both a gene in cis and in trans suggests that the cis gene is functionally linked to the trans gene expression, we looked specifically for trans effects of cis-eQTLs. We discovered that 26 cis-eQTLs are associated to 92 genes in trans with the cis-eQTLs of the transcriptions factors BATF3 and HMX2 affecting the most genes. We then explored if the variation of the level of expression of the cis genes were causally affecting the level of expression of the trans genes and discovered several causal relationships between variation in the level of expression of the cis gene and variation of the level of expression of the trans gene. This analysis shows that a large sample size allows the discovery of secondary effects of human variations on gene expression that can be used to construct short directed gene regulatory networks. |
| format | Article |
| id | doaj-art-5b10848653504b0bb99478d73cd32368 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-5b10848653504b0bb99478d73cd323682025-08-20T03:46:43ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-07-01107e100446110.1371/journal.pgen.1004461Cis and trans effects of human genomic variants on gene expression.Julien BryoisAlfonso BuilDavid M EvansJohn P KempStephen B MontgomeryDonald F ConradKaren M HoSusan RingMatthew HurlesPanos DeloukasGeorge Davey SmithEmmanouil T DermitzakisGene expression is a heritable cellular phenotype that defines the function of a cell and can lead to diseases in case of misregulation. In order to detect genetic variations affecting gene expression, we performed association analysis of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with gene expression measured in 869 lymphoblastoid cell lines of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in cis and in trans. We discovered that 3,534 genes (false discovery rate (FDR) = 5%) are affected by an expression quantitative trait locus (eQTL) in cis and 48 genes are affected in trans. We observed that CNVs are more likely to be eQTLs than SNPs. In addition, we found that variants associated to complex traits and diseases are enriched for trans-eQTLs and that trans-eQTLs are enriched for cis-eQTLs. As a variant affecting both a gene in cis and in trans suggests that the cis gene is functionally linked to the trans gene expression, we looked specifically for trans effects of cis-eQTLs. We discovered that 26 cis-eQTLs are associated to 92 genes in trans with the cis-eQTLs of the transcriptions factors BATF3 and HMX2 affecting the most genes. We then explored if the variation of the level of expression of the cis genes were causally affecting the level of expression of the trans genes and discovered several causal relationships between variation in the level of expression of the cis gene and variation of the level of expression of the trans gene. This analysis shows that a large sample size allows the discovery of secondary effects of human variations on gene expression that can be used to construct short directed gene regulatory networks.https://doi.org/10.1371/journal.pgen.1004461 |
| spellingShingle | Julien Bryois Alfonso Buil David M Evans John P Kemp Stephen B Montgomery Donald F Conrad Karen M Ho Susan Ring Matthew Hurles Panos Deloukas George Davey Smith Emmanouil T Dermitzakis Cis and trans effects of human genomic variants on gene expression. PLoS Genetics |
| title | Cis and trans effects of human genomic variants on gene expression. |
| title_full | Cis and trans effects of human genomic variants on gene expression. |
| title_fullStr | Cis and trans effects of human genomic variants on gene expression. |
| title_full_unstemmed | Cis and trans effects of human genomic variants on gene expression. |
| title_short | Cis and trans effects of human genomic variants on gene expression. |
| title_sort | cis and trans effects of human genomic variants on gene expression |
| url | https://doi.org/10.1371/journal.pgen.1004461 |
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