Genome-wide analyses indirectly implicate miRNA regulatory mechanisms in Obsessive-compulsive Disorder psychopathology
作者： NW McGregor , KS O’Connell , L Davis , CA Mathews , C Lochner
DOI: 10.1101/601401
关键词: Genetics 、 Disease 、 Biology 、 microRNA 、 Immune dysregulation 、 Psychopathology 、 Gene expression 、 MiRBase 、 Regulation of gene expression 、 Single-nucleotide polymorphism
摘要: ABSTRACT Background MiRNAs are small, noncoding RNAs possessing the potential to modulate gene expression upon binding their target messenger RNA (mRNA) constructs, and known play a role in pathogenesis of range psychiatric disorders. To date, little work has focused on miRNAs obsessive-compulsive disorder (OCD). The aim this study was assess involvement OCD psychopathology. Methods most significant variants (p ≤ 1×10−4) from Psychiatric Genomics Consortium (PGC) TS/OCD Workgroup meta-analysis were selected investigated using miRBASE, TargetScan SNPnexus determine whether they influence miRNA- mediated regulation clinical manifestation OCD. Results Two-hundred forty SNPs identified PGC summarystatistics, which none found directly alter miRNA-related silico analyses. Enrichment analyses several indirect miRNA-mediated targets associated with both increased (ITPR3: mir-124A) decreased risk (GPR109A: mir-520A, mir-525; CGNL1: mir-98 mir-219). Conclusion indirectly implicated psychopathology implicates intracellular calcium immune dysregulation warrants further investigation system may disease.
sci-hub.st 参考文章(43)
Robin Emsley, Laila Asmal, Stéfan du Plessis, Bonginkosi Chiliza, Martin Kidd, Jonathan Carr, Matthijs Vink, Dorsal striatal volumes in never-treated patients with first-episode schizophrenia before and during acute treatment Schizophrenia Research. ,vol. 169, pp. 89- 94 ,(2015) , 10.1016/J.SCHRES.2015.09.014
Dimitrios Avramopoulos, Brad D. Pearce, John McGrath, Paula Wolyniec, Ruihua Wang, Nicole Eckart, Alexandros Hatzimanolis, Fernando S. Goes, Gerald Nestadt, Jennifer Mulle, Karen Coneely, Myfanwy Hopkins, Ingo Ruczinski, Robert Yolken, Ann E. Pulver, Infection and Inflammation in Schizophrenia and Bipolar Disorder: A Genome Wide Study for Interactions with Genetic Variation PLOS ONE. ,vol. 10, ,(2015) , 10.1371/JOURNAL.PONE.0116696
Chandramohan Wakade, Raymond Chong, A novel treatment target for Parkinson's disease Journal of the Neurological Sciences. ,vol. 347, pp. 34- 38 ,(2014) , 10.1016/J.JNS.2014.10.024
Teri A Manolio, Francis S Collins, Nancy J Cox, David B Goldstein, Lucia A Hindorff, David J Hunter, Mark I McCarthy, Erin M Ramos, Lon R Cardon, Aravinda Chakravarti, Judy H Cho, Alan E Guttmacher, Augustine Kong, Leonid Kruglyak, Elaine Mardis, Charles N Rotimi, Montgomery Slatkin, David Valle, Alice S Whittemore, Michael Boehnke, Andrew G Clark, Evan E Eichler, Greg Gibson, Jonathan L Haines, Trudy FC Mackay, Steven A McCarroll, Peter M Visscher, None, Finding the missing heritability of complex diseases. Nature. ,vol. 461, pp. 747- 753 ,(2009) , 10.1038/NATURE08494
Palanikumar Manoharan, Joshua E. Basford, Robyn Pilcher-Roberts, Jonathan Neumann, David Y. Hui, Jerry B. Lingrel, Reduced Levels of microRNAs miR-124a and miR-150 Are Associated with Increased Proinflammatory Mediator Expression in Krüppel-like Factor 2 (KLF2)-deficient Macrophages Journal of Biological Chemistry. ,vol. 289, pp. 31638- 31646 ,(2014) , 10.1074/JBC.M114.579763
M Mattheisen, J F Samuels, Y Wang, B D Greenberg, A J Fyer, J T McCracken, D A Geller, D L Murphy, J A Knowles, M A Grados, M A Riddle, S A Rasmussen, N C McLaughlin, E L Nurmi, K D Askland, H-D Qin, B A Cullen, J Piacentini, D L Pauls, O J Bienvenu, S E Stewart, K-Y Liang, F S Goes, B Maher, A E Pulver, Y Y Shugart, D Valle, C Lange, G Nestadt, Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS Molecular Psychiatry. ,vol. 20, pp. 337- 344 ,(2015) , 10.1038/MP.2014.43
Stefan Offermanns, Markus Schwaninger, Nutritional or pharmacological activation of HCA2 ameliorates neuroinflammation Trends in Molecular Medicine. ,vol. 21, pp. 245- 255 ,(2015) , 10.1016/J.MOLMED.2015.02.002
P M Visscher, M E Goddard, E M Derks, N R Wray, Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses. Molecular Psychiatry. ,vol. 17, pp. 474- 485 ,(2012) , 10.1038/MP.2011.65
Joshua G. Hunsberger, Daniel R. Austin, Guang Chen, Husseini K. Manji, MicroRNAs in Mental Health: From Biological Underpinnings to Potential Therapies Neuromolecular Medicine. ,vol. 11, pp. 173- 182 ,(2009) , 10.1007/S12017-009-8070-5
Rachel H.B. Mitchell, Benjamin I. Goldstein, Inflammation in Children and Adolescents With Neuropsychiatric Disorders: A Systematic Review Journal of the American Academy of Child & Adolescent Psychiatry. ,vol. 53, pp. 274- 296 ,(2014) , 10.1016/J.JAAC.2013.11.013