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Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression
- Source :
- PLoS ONE; Vol 7, PLoS ONE, PLoS ONE, Vol 7, Iss 12, p e52260 (2012)
- Publication Year :
- 2012
- Publisher :
- Uppsala universitet, Molekylär medicin, 2012.
-
Abstract
- 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.
- Subjects :
- Medicin och hälsovetenskap
genetic association
Microarrays
genotype
lcsh:Medicine
Gene Expression
Genome-wide association study
genotyping expression analysis
genetic analysis
Regulatory Sequences, Nucleic Acid
Medical and Health Sciences
Monocytes
0302 clinical medicine
Gene Frequency
single nucleotide polymorphism
lcsh:Science
Genetics
0303 health sciences
Multidisciplinary
messenger RNA
article
Chromosome Mapping
Genomics
sample size
Functional Genomics
quantitative trait locus mapping
monocyte
allele specific gene expression analysis
Research Article
Genetic Markers
Genotype
Quantitative Trait Loci
DNA flanking region
Single-nucleotide polymorphism
Biology
gene frequency
Polymorphism, Single Nucleotide
03 medical and health sciences
Gene mapping
Genome Analysis Tools
Genetic Mutation
Genome-Wide Association Studies
Humans
RNA, Messenger
human
Allele
blood donor
intermethod comparison
Allele frequency
Genetic Association Studies
Alleles
030304 developmental biology
Gene Expression Profiling
human cell
lcsh:R
Computational Biology
Human Genetics
gene mapping
Gene expression profiling
Minor allele frequency
Gene Expression Regulation
Expression quantitative trait loci
Genetic Polymorphism
gene expression
lcsh:Q
Genome Expression Analysis
Population Genetics
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE; Vol 7, PLoS ONE, PLoS ONE, Vol 7, Iss 12, p e52260 (2012)
- Accession number :
- edsair.doi.dedup.....0c26502286334aa82a5f081f2917b2ea