ArticlePLoS genetics2008
Modifier effects between regulatory and protein-coding variation.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Molecular evolution in light of regulatory-coding epistasis.EMBO reports · 2026Review
- A 20 Bp Indel ofAnimals : an open access journal from MDPI · 2026Article
- The genetic basis of mimicry in the snowy bumble bee (Bombus niveatus) in Anatolia with insights from a color polymorphic gynandromorph.PLoS genetics · 2026Article
- Gain of Alternative Allele Expression of LINC02449 at rs149707223 in Schizophrenia and Bipolar Disorder: Inducing Synaptic Transmission and Behavioral Deficits in Mice.Nature communications · 2025Article
- Article
- Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk.Nature genetics · 2018Article
- Enhanced methods to detect haplotypic effects on gene expression.Bioinformatics (Oxford, England) · 2017Article
- Multikernel linear mixed models for complex phenotype prediction.Genome research · 2016Article
- Analyzing allele specific RNA expression using mixture models.BMC genomics · 2015Article
- Disruption of long-range gene regulation in human genetic disease: a kaleidoscope of general principles, diverse mechanisms and unique phenotypic consequences.Human genetics · 2014Review
- Random forest fishing: a novel approach to identifying organic group of risk factors in genome-wide association studies.European journal of human genetics : EJHG · 2014Article
- Genetic and epigenetic regulation of human lincRNA gene expression.American journal of human genetics · 2013Article
- Detection and impact of rare regulatory variants in human disease.Frontiers in genetics · 2013Article
- Epistatic selection between coding and regulatory variation in human evolution and disease.American journal of human genetics · 2011Article
- Rare and common regulatory variation in population-scale sequenced human genomes.PLoS genetics · 2011Article
- Using stochastic causal trees to augment Bayesian networks for modeling eQTL datasets.BMC bioinformatics · 2011Article
- Comparison of strategies to detect epistasis from eQTL data.PloS one · 2011Article
- Performance of single nucleotide polymorphisms versus haplotypes for genome-wide association analysis in barley.PloS one · 2010Article
- Data analysis issues for allele-specific expression using Illumina's GoldenGate assay.BMC bioinformatics · 2010Article
- Linking variants from genome-wide association analysis to function via transcriptional network analysis.Seminars in nephrology · 2010Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.