Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression.
A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3530574?pdf=render |
| _version_ | 1819126513226743808 |
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| author | Jonas Carlsson Almlöf Per Lundmark Anders Lundmark Bing Ge Seraya Maouche Harald H H Göring Ulrika Liljedahl Camilla Enström Jessy Brocheton Carole Proust Tiphaine Godefroy Jennifer G Sambrook Jennifer Jolley Abigail Crisp-Hihn Nicola Foad Heather Lloyd-Jones Jonathan Stephens Rhian Gwilliam Catherine M Rice Christian Hengstenberg Nilesh J Samani Jeanette Erdmann Heribert Schunkert Tomi Pastinen Panos Deloukas Alison H Goodall Willem H Ouwehand François Cambien Ann-Christine Syvänen |
| author_facet | Jonas Carlsson Almlöf Per Lundmark Anders Lundmark Bing Ge Seraya Maouche Harald H H Göring Ulrika Liljedahl Camilla Enström Jessy Brocheton Carole Proust Tiphaine Godefroy Jennifer G Sambrook Jennifer Jolley Abigail Crisp-Hihn Nicola Foad Heather Lloyd-Jones Jonathan Stephens Rhian Gwilliam Catherine M Rice Christian Hengstenberg Nilesh J Samani Jeanette Erdmann Heribert Schunkert Tomi Pastinen Panos Deloukas Alison H Goodall Willem H Ouwehand François Cambien Ann-Christine Syvänen |
| author_sort | Jonas Carlsson Almlöf |
| collection | DOAJ |
| description | A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers. |
| first_indexed | 2024-12-22T07:57:13Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:57:13Z |
| publishDate | 2012-01-01 |
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| spelling | doaj.art-d0a286581c23430fa9c2b3d1ada6f11f2022-12-21T18:33:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5226010.1371/journal.pone.0052260Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression.Jonas Carlsson AlmlöfPer LundmarkAnders LundmarkBing GeSeraya MaoucheHarald H H GöringUlrika LiljedahlCamilla EnströmJessy BrochetonCarole ProustTiphaine GodefroyJennifer G SambrookJennifer JolleyAbigail Crisp-HihnNicola FoadHeather Lloyd-JonesJonathan StephensRhian GwilliamCatherine M RiceChristian HengstenbergNilesh J SamaniJeanette ErdmannHeribert SchunkertTomi PastinenPanos DeloukasAlison H GoodallWillem H OuwehandFrançois CambienAnn-Christine SyvänenA large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.http://europepmc.org/articles/PMC3530574?pdf=render |
| spellingShingle | Jonas Carlsson Almlöf Per Lundmark Anders Lundmark Bing Ge Seraya Maouche Harald H H Göring Ulrika Liljedahl Camilla Enström Jessy Brocheton Carole Proust Tiphaine Godefroy Jennifer G Sambrook Jennifer Jolley Abigail Crisp-Hihn Nicola Foad Heather Lloyd-Jones Jonathan Stephens Rhian Gwilliam Catherine M Rice Christian Hengstenberg Nilesh J Samani Jeanette Erdmann Heribert Schunkert Tomi Pastinen Panos Deloukas Alison H Goodall Willem H Ouwehand François Cambien Ann-Christine Syvänen Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression. PLoS ONE |
| title | Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression. |
| title_full | Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression. |
| title_fullStr | Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression. |
| title_full_unstemmed | Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression. |
| title_short | Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression. |
| title_sort | powerful identification of cis regulatory snps in human primary monocytes using allele specific gene expression |
| url | http://europepmc.org/articles/PMC3530574?pdf=render |
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