MirSNP, a Database of Polymorphisms Altering MiRNA Target Sites, Identifies MiRNA-related SNPs in GWAS SNPs and EQTLs

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2012 Nov 24

PMID 23173617

Citations 137

Authors

Chenxing Liu

Fuquan Zhang

Tingting Li

Ming Lu

Lifang Wang

Weihua Yue

Dai Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Numerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3'UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3'UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers.

Description: We developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398), which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p < 0.0001) were found in the schizophrenia GWAS. Our findings identified the possible functions of these SNP loci, and provide the basis for subsequent functional research.

Conclusion: MirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.

Citing Articles

Influence of rs Genetic Variant on miR-21 Gene Expression in Patients With Type 1 Diabetes Mellitus: A Case-Control Study.

Bayat R, Salehi Z, Dalili S, Mashayekhi F Health Sci Rep. 2025; 8(3):e70480.

PMID: 40041782 PMC: 11872810. DOI: 10.1002/hsr2.70480.

The melanocortin receptor genes are linked to and associated with the risk of polycystic ovary syndrome in Italian families.

Wu R, Gragnoli C J Ovarian Res. 2024; 17(1):242.

PMID: 39633478 PMC: 11619144. DOI: 10.1186/s13048-024-01567-1.

Implication of vasopressin receptor genes (AVPR1A and AVPR1B) in the susceptibility to polycystic ovary syndrome.

Goparaju P, Gragnoli C J Ovarian Res. 2024; 17(1):214.

PMID: 39501331 PMC: 11536872. DOI: 10.1186/s13048-024-01515-z.

Exosomal miR-155-5p promote the occurrence of carotid atherosclerosis.

Yang W, Li Q, Wang F, Zhang X, Zhang X, Wang M J Cell Mol Med. 2024; 28(21):e70187.

PMID: 39495676 PMC: 11534067. DOI: 10.1111/jcmm.70187.

Screening and analysis of single nucleotide polymorphism in the 3'-UTR microRNA target regions and its implications for lung tumorigenesis.

Bhatia A, Upadhyay A, Sharma S Pharmacogenomics. 2024; 25(7):299-314.

PMID: 38884942 PMC: 11404702. DOI: 10.1080/14622416.2024.2355864.

References

Alexiou P, Maragkakis M, Papadopoulos G, Reczko M, Hatzigeorgiou A . Lost in translation: an assessment and perspective for computational microRNA target identification. Bioinformatics. 2009; 25(23):3049-55. DOI: 10.1093/bioinformatics/btp565. View

Voinnet O . Origin, biogenesis, and activity of plant microRNAs. Cell. 2009; 136(4):669-87. DOI: 10.1016/j.cell.2009.01.046. View

Sherry S, Ward M, Kholodov M, Baker J, Phan L, Smigielski E . dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2000; 29(1):308-11. PMC: 29783. DOI: 10.1093/nar/29.1.308. View

Thomas L, Saito T, Saetrom P . Inferring causative variants in microRNA target sites. Nucleic Acids Res. 2011; 39(16):e109. PMC: 3167593. DOI: 10.1093/nar/gkr414. View

Betel D, Wilson M, Gabow A, Marks D, Sander C . The microRNA.org resource: targets and expression. Nucleic Acids Res. 2007; 36(Database issue):D149-53. PMC: 2238905. DOI: 10.1093/nar/gkm995. View

Ziebarth J, Bhattacharya A, Chen A, Cui Y . PolymiRTS Database 2.0: linking polymorphisms in microRNA target sites with human diseases and complex traits. Nucleic Acids Res. 2011; 40(Database issue):D216-21. PMC: 3245163. DOI: 10.1093/nar/gkr1026. View

Krol J, Loedige I, Filipowicz W . The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010; 11(9):597-610. DOI: 10.1038/nrg2843. View

Gibbs J, van der Brug M, Hernandez D, Traynor B, Nalls M, Lai S . Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genet. 2010; 6(5):e1000952. PMC: 2869317. DOI: 10.1371/journal.pgen.1000952. View

He L, Hannon G . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522-31. DOI: 10.1038/nrg1379. View

10.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

11.

Lewis B, Burge C, Bartel D . Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005; 120(1):15-20. DOI: 10.1016/j.cell.2004.12.035. View

12.

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira M, Bender D . PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007; 81(3):559-75. PMC: 1950838. DOI: 10.1086/519795. View

13.

Yue W, Wang H, Sun L, Tang F, Liu Z, Zhang H . Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet. 2011; 43(12):1228-31. DOI: 10.1038/ng.979. View

14.

Yang L, Li Y, Cheng M, Huang D, Zheng J, Liu B . A functional polymorphism at microRNA-629-binding site in the 3'-untranslated region of NBS1 gene confers an increased risk of lung cancer in Southern and Eastern Chinese population. Carcinogenesis. 2011; 33(2):338-47. DOI: 10.1093/carcin/bgr272. View

15.

Barenboim M, Zoltick B, Guo Y, Weinberger D . MicroSNiPer: a web tool for prediction of SNP effects on putative microRNA targets. Hum Mutat. 2010; 31(11):1223-32. PMC: 3001138. DOI: 10.1002/humu.21349. View

16.

Gao F . Posttranscriptional control of neuronal development by microRNA networks. Trends Neurosci. 2007; 31(1):20-6. PMC: 3545480. DOI: 10.1016/j.tins.2007.10.004. View

17.

Cho S, Jun Y, Lee S, Choi H, Jung S, Jang Y . miRGator v2.0: an integrated system for functional investigation of microRNAs. Nucleic Acids Res. 2010; 39(Database issue):D158-62. PMC: 3013691. DOI: 10.1093/nar/gkq1094. View

18.

Sethupathy P, Collins F . MicroRNA target site polymorphisms and human disease. Trends Genet. 2008; 24(10):489-97. DOI: 10.1016/j.tig.2008.07.004. View

19.

Berezikov E . Evolution of microRNA diversity and regulation in animals. Nat Rev Genet. 2011; 12(12):846-60. DOI: 10.1038/nrg3079. View

20.

Siepel A, Bejerano G, Pedersen J, Hinrichs A, Hou M, Rosenbloom K . Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005; 15(8):1034-50. PMC: 1182216. DOI: 10.1101/gr.3715005. View