ArticleNucleic acids research2013
Resolving the polymorphism-in-probe problem is critical for correct interpretation of expression QTL studies.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Genetic regulation of gene expression in the epileptic human hippocampus.Human molecular genetics · 2017Pooled it
- A meta-analysis of gene expression quantitative trait loci in brain.Translational psychiatry · 2014Pooled it
- Bayesian test for colocalisation between pairs of genetic association studies using summary statistics.PLoS genetics · 2014Pooled it
- The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen-receptor positive tumors.Molecular oncology · 2014Trial
- Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study.Brain : a journal of neurology · 2021Article
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- Targeted sequencing of the LRRTM gene family in suicide attempters with bipolar disorder.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020Article
- DLPFC transcriptome defines two molecular subtypes of schizophrenia.Translational psychiatry · 2019Article
- Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability.NPJ Parkinson's disease · 2019Article
- Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue.PLoS genetics · 2018Article
- A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver.Scientific reports · 2018Article
- Inbred Strain Variant Database (ISVdb): A Repository for Probabilistically Informed Sequence Differences Among the Collaborative Cross Strains and Their Founders.G3 (Bethesda, Md.) · 2017Article
- Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies.Genome biology · 2017Article
- Gene regulatory effects of disease-associated variation in the NRF2 network.Current opinion in toxicology · 2016Article
- Comprehensive promoter level expression quantitative trait loci analysis of the human frontal lobe.Genome medicine · 2016Article
- A Polymorphic Antioxidant Response Element Links NRF2/sMAF Binding to Enhanced MAPT Expression and Reduced Risk of Parkinsonian Disorders.Cell reports · 2016Article
- Observational
- Gene expression markers of age-related inflammation in two human cohorts.Experimental gerontology · 2015Article
- Equalizer reduces SNP bias in Affymetrix microarrays.BMC bioinformatics · 2015Article
- Article
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Polymorphisms in the target mRNA sequence can greatly affect the binding affinity of microarray probe sequences, leading to false-positive and false-negative expression quantitative trait locus (QTL) signals with any other polymorphisms in linkage disequilibrium. We provide the most complete solution to this problem, by using the latest genome and exome sequence reference data to identify almost all common polymorphisms (frequency >1% in Europeans) in probe sequences for two commonly used microarray panels (the gene-based Illumina Human HT12 array, which uses 50-mer probes, and exon-based Affymetrix Human Exon 1.0 ST array, which uses 25-mer probes). We demonstrate the impact of this problem using cerebellum and frontal cortex tissues from 438 neuropathologically normal individuals. We find that although only a small proportion of the probes contain polymorphisms, they account for a large proportion of apparent expression QTL signals, and therefore result in many false signals being declared as real. We find that the polymorphism-in-probe problem is insufficiently controlled by previous protocols, and illustrate this using some notable false-positive and false-negative examples in MAPT and PRICKLE1 that can be found in many eQTL databases. We recommend that both new and existing eQTL data sets should be carefully checked in order to adequately address this issue.
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