Population differences in transcript-regulator expression quantitative trait loci.
Gene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regul...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0034286&type=printable |
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| author | Pierre R Bushel Ray McGovern Liwen Liu Oliver Hofmann Ahsan Huda Jun Lu Winston Hide Xihong Lin |
| author_facet | Pierre R Bushel Ray McGovern Liwen Liu Oliver Hofmann Ahsan Huda Jun Lu Winston Hide Xihong Lin |
| author_sort | Pierre R Bushel |
| collection | DOAJ |
| description | Gene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator (TR). We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African (YRI) HapMap populations. A nominal p-value of <1×10(-6) revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene) in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP (rs3790904) in CEU maps to Lphn2 and is associated (nominal p-value = 8.1×10(-7)) with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis. |
| format | Article |
| id | doaj-art-52236a6d3b684166bf220c6c40eedfcc |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-52236a6d3b684166bf220c6c40eedfcc2025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3428610.1371/journal.pone.0034286Population differences in transcript-regulator expression quantitative trait loci.Pierre R BushelRay McGovernLiwen LiuOliver HofmannAhsan HudaJun LuWinston HideXihong LinGene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator (TR). We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African (YRI) HapMap populations. A nominal p-value of <1×10(-6) revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene) in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP (rs3790904) in CEU maps to Lphn2 and is associated (nominal p-value = 8.1×10(-7)) with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0034286&type=printable |
| spellingShingle | Pierre R Bushel Ray McGovern Liwen Liu Oliver Hofmann Ahsan Huda Jun Lu Winston Hide Xihong Lin Population differences in transcript-regulator expression quantitative trait loci. PLoS ONE |
| title | Population differences in transcript-regulator expression quantitative trait loci. |
| title_full | Population differences in transcript-regulator expression quantitative trait loci. |
| title_fullStr | Population differences in transcript-regulator expression quantitative trait loci. |
| title_full_unstemmed | Population differences in transcript-regulator expression quantitative trait loci. |
| title_short | Population differences in transcript-regulator expression quantitative trait loci. |
| title_sort | population differences in transcript regulator expression quantitative trait loci |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0034286&type=printable |
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