ArticlePloS one2012
Cis-acting polymorphisms affect complex traits through modifications of microRNA regulation pathways.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- The miRNA-target interactions: An underestimated intricacy.Nucleic acids research · 2024Review
- Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer.Molecular genetics and genomics : MGG · 2022Article
- The Association of ATG16L1 Variations with Clinical Phenotypes of Adult-Onset Still's Disease.Genes · 2021Article
- Determination of the effect of functional single-nucleotide polymorphisms associated with glycerolipid synthesis on intramuscular fat deposition in Korean cattle steer.Archives animal breeding · 2021Article
- A Functional riboSNitch in the 3' Untranslated Region ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell functional maturity.Cell death & disease · 2018Article
- A PLAG1 mutation contributed to stature recovery in modern cattle.Scientific reports · 2017Article
- Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD).International journal of molecular sciences · 2017Article
- Variation in the αPharmacogenomics · 2017Article
- Condylar geometry variation is associated with ENPP1 variant in a population of patients with dento-facial deformities.Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery · 2017Article
- The roles of RNA processing in translating genotype to phenotype.Nature reviews. Molecular cell biology · 2017Review
- Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity.Clinical reviews in allergy & immunology · 2016Review
- Review
- Proteostasis and RNA Binding Proteins in Synaptic Plasticity and in the Pathogenesis of Neuropsychiatric Disorders.Neural plasticity · 2016Review
- Article
- Heterogeneity and individuality: microRNAs in mental disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2015Review
- Non-coding RNAs and lipid metabolism.International journal of molecular sciences · 2014Review
- Mining the 3'UTR of autism-implicated genes for SNPs perturbing microRNA regulation.Genomics, proteomics & bioinformatics · 2014Article
- MicroRNAs in the onset and development of cardiovascular disease.Clinical science (London, England : 1979) · 2014Review
- Alternative polyadenylation and differential expression of Shank mRNAs in the synaptic neuropil.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWAS) have become an effective tool to map genes and regions contributing to multifactorial human diseases and traits. A comparably small number of variants identified by GWAS are known to have a direct effect on protein structure whereas the majority of variants is thought to exert their moderate influences on the phenotype through regulatory changes in mRNA expression. MicroRNAs (miRNAs) have been identified as powerful posttranscriptional regulators of mRNAs. Binding to their target sites, which are mostly located within the 3'-untranslated region (3'-UTR) of mRNA transcripts, they modulate mRNA expression and stability. Until today almost all human mRNA transcripts are known to harbor at least one miRNA target site with an average of over 20 miRNA target sites per transcript. Among 5,101 GWAS-identified sentinel single nucleotide polymorphisms (SNPs) that correspond to 18,884 SNPs in linkage disequilibrium (LD) with the sentinels (r2 ≥ 0.8) we identified a significant overrepresentation of SNPs that affect the 3'-UTR of genes (OR = 2.33, 95% CI = 2.12-2.57, P < 10(-52)). This effect was even stronger considering all SNPs in one LD bin a single signal (OR = 4.27, 95% CI = 3.84-4.74, P < 10(-114)). Based on crosslinking immunoprecipitation data we identified four mechanisms affecting miRNA regulation by 3'-UTR mutations: (i) deletion or (ii) creation of miRNA recognition elements within validated RNA-induced silencing complex binding sites, (iii) alteration of 3'-UTR splicing leading to a loss of binding sites, and (iv) change of binding affinity due to modifications of 3'-UTR folding. We annotated 53 SNPs of a total of 288 trait-associated 3'-UTR SNPs as mediating at least one of these mechanisms. Using a qualitative systems biology approach, we demonstrate how our findings can be used to support biological interpretation of GWAS results as well as to provide new experimentally testable hypotheses.
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