Journal of Isfahan Medical School

Journal of Isfahan Medical School

Investigation of Structural Patterns in the Gene Expression Network of Patients with Obsessive-Compulsive Disorder

Document Type : Original Article (s)

Authors
Masoumeh Rashno
Fatemeh Bossaghzadeh
Zahra Khoshnood
Assistant Professor, Department of Biology, Dezful Branch, Islamic Azad University, Dezful, Iran
10.48305/jims.v43.i813.0429
Abstract
Background: Obsessive compulsive disorder is a multifaceted psychiatric condition characterized by intrusive thoughts and compulsive behaviors. Genetic factors are one of the main causes of this disorder. By examining the structural patterns in the gene expression network of patients, this study uses a comprehensive weighted gene co-expression network analysis (WGCNA) to clarify the underlying molecular mechanisms of this disorder.
Methods: This study was done analytically on gene expression data from obsessive-compulsive disorder patients compared to a control group (healthy people). Candidate genes involved in the disease, proposed based on at least one method (in vivo, in vitro, or in silico), were extracted from the bioinformatics databases NCBI, GeneCards, Swiss-Prot, and Diseasome. Then, expression data were collected from in vivo, in vitro and in silico studies, and communication networks were drawn from the expression data of candidate genes using MATLAB and R software.
Findings: Based on the results of candidate protein communication network analysis, with the help of 5 component indicators of the highest degree of neighborhood, degree, distance, proximity and radius respectively, the 6 proteins SOX9, ACAN, RUNX2, COL1A1, COL2A1 and MMP13 had the highest frequency of being identified by these 5 metrics.
Conclusion: The structural patterns in the gene expression network showed that SOX9, ACAN, RUNX2, COL1A1, COL2A1, and MMP13 genes are particularly important in obsessive-compulsive patients compared to other candidate genes. This finding could aid in the development and analysis of a diagnostic gene panel for this disorder.

Highlights

Zahra Khoshnood: Google Scholar, PubMed

Keywords
Obsessive-compulsive patients
Structural patterns
Gene expression network
Subjects
  1. Zai G, Barta C, Cath D, Eapen V, Geller D, Grünblatt E. New insights and perspectives on the genetics of obsessive-compulsive disorder. Psychiatr Genet 2019; 29(5): 142-51.
  2. Strom NI, Soda T, Mathews CA, Davis LK. A dimensional perspective on the genetics of obsessive-compulsive disorder. Transl Psychiatry 2021; 11(1): 401.
  3. Stein D, Costa D, Lochner C, Miguel E, Reddy Y, Shavitt R, et al. Obsessive-compulsive disorder. Nat Rev Dis Primers 2019; 5(1): 52. 2019.
  4. Taylor S. Early versus late onset obsessive–compulsive disorder: evidence for distinct subtypes. Clin Psychol Rev 2011; 31(7): 1083-100.
  5. Teixeira J, Carvalho I, Pires P. 706–110 years after first report of obsessive compulsive disorder in childhood-where do we stand? European Psychiatry 2013; 28(Suppl 1): 1.
  6. Anholt GE, Aderka IM, van Balkom AJLM, Smit JH, Schruers K, van Der Wee NJA, et al. Age of onset in obsessive–compulsive disorder: admixture analysis with a large sample. Psychol Med 2014; 44(1): 185-94.
  7. Browne HA, Gair SL, Scharf JM, Grice DE. Genetics of obsessive-compulsive disorder and related disorders. Psychiatr Clin North Am 2014; 37(3): 319-35.
  8. Mattina GF, Steiner M. The need for inclusion of sex and age of onset variables in genetic association studies of obsessive–compulsive disorder: Overview. Prog Neuropsychopharmacol Biol Psychiatry 2016; 67: 107-16.
  9. Blanco-Vieira T, Radua J, Marcelino L, Bloch M, Mataix-Cols D, do Rosário MC. The genetic epidemiology of obsessive-compulsive disorder: a systematic review and meta-analysis. Transl Psychiatry 2023; 13(1): 230.
  10. Goodman WK, Storch EA, Sheth SA. Harmonizing the neurobiology and treatment of obsessive-compulsive disorder. Am J Psychiatry 2021; 178(1): 17-29.
  11. Fernandez TV, Leckman JF, Pittenger C. Genetic susceptibility in obsessive-compulsive disorder. Handb Clin Neurol 2018; 148: 767-81.
  12. Gerring ZF, Thorp JG, Gamazon ER, Derks EM. A systematic analysis of genetically regulated differences in gene expression and the role of co-expression networks across 16 psychiatric disorders and substance use phenotypes. Eur J Hum Genet 2022; 30(5): 560-6.
  13. Castro Martínez JC, Santamaría-García H. Understanding mental health through computers: An introduction to computational psychiatry. Front Psychiatry 2023; 14: 1092471.
  14. Hijazo-Pechero S, Alay A, Marín R, Vilariño N, Muñoz-Pinedo C, Villanueva A, et al. Gene expression profiling as a potential tool for precision oncology in non-small cell lung cancer. Cancers (Basel) 2021; 13.
  15. Shephard E, Batistuzzo MC, Hoexter MQ, Stern ER, Zuccolo PF, Ogawa CY, et al. Neurocircuit models of obsessive-compulsive disorder: limitations and future directions for research. Braz J Psychiatry 2022; 44(2): 187-200.
  16. Ferreri F, Bourla A, Peretti CS, Segawa T, Jaafari N, Mouchabac S. How New Technologies Can Improve Prediction, Assessment, and Intervention in Obsessive-Compulsive Disorder (e-OCD): Review. JMIR Ment Health 2019; 6(12): e11643.
  17. Carels N, Sgariglia D, Junior MGV, Lima CR, Carneiro FRG, Silva GFD, et al. A strategy utilizing protein-protein interaction hubs for the treatment of cancer diseases. Int J Mol Sci 2023; 24(22): 16098.
  18. Soni M, Bhatt MW, Asenso E, Jhon DMO. Gene prioritization-based active bio-module identification for bioinformatics. Scientific African 2024; 26: e02466.
  19. Oehlers M, Fabian B. Graph Metrics for Network Robustness—A Survey. Mathematics 2021; 9(8): 895.
  20. Barton S, Broad Z, Ortiz-Barrientos D, Donovan D, Lefevre J. Hypergraphs and centrality measures identifying key features in gene expression data. Math Biosci 2023; 366: 109089.
  21. Starcevic V, Eslick GD, Viswasam K, Berle D. Symptoms of obsessive-compulsive disorder during pregnancy and the postpartum period: A systematic review and meta-analysis. Psychiatr Q 2020; 91(4): 965-81.
  22. Zhang X, Liu Y, Guo B, Li B, Liu H, Wang Z. Identification of key mRNAs and signaling pathways in obsessive compulsive disorder based on weighted gene co‐expression network analysis and cytoHubba plugin. Brain Behav 2024; 14(5): e3412.
  23. Song W, Wang W, Yu S, Lin GN. Dissection of the genetic association between anorexia nervosa and obsessive–compulsive disorder at the network and cellular levels. Genes (Basel) 2021; 12(4): 491.
  24. Strom NI, Halvorsen MW, Tian C, Rück C, Kvale G, Hansen B, et al. Genome-wide association study identifies new loci associated with OCD. medRxiv 2024.
  25. Rodríguez N, Lázaro L, Ortiz AE, Morer A, Martínez-Pinteño A, Segura AG, et al. Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder. Transl Psychiatry 2022; 12(1): 134.
  26. Ming Z, Vining B, Bagheri-Fam S, Harley V. SOX9 in organogenesis: shared and unique transcriptional functions. Cell Mol Life Sci 2022; 79(10): 522.
  27. Tsetsos F, Topaloudi A, Jain P, Yang Z, Yu D, Kolovos P, et al. Genome-wide Association Study identifies two novel loci for Gilles de la Tourette Syndrome. Biol Psychiatry 2024; 96(2): 114-24.
  28. Jeon SJ, Ryu JH, Bahn GH. Altered translational control of fragile X mental retardation protein on myelin proteins in neuropsychiatric disorders. Biomol Ther (Seoul) 2017; 25(3): 231-8.
  29. Tang W, Wu KM, Zhou Q, Tang YF, Fu JF, Dong GP, Zou CC. Genotype and phenotype in patients with ACAN gene variants: Three cases and literature review. Mol Genet Genomic Med 2024; 12(4): e2439.
  30. Uchida N, Shibata H, Nishimura G, Hasegawa T. A novel mutation in the ACAN gene in a family with autosomal dominant short stature and intervertebral disc disease. Hum Genome Var 2020; 7(1): 44.
  31. Gug C, Caba L, Mozos I, Stoian D, Atasie D, Gug M, Gorduza EV. Rare splicing mutation in COL1A1 gene identified by whole exomes sequencing in a patient with osteogenesis imperfecta type I followed by prenatal diagnosis: A case report and review of the literature. Gene 2020; 741: 144565.
  32. Zeweil MM, Sadek KM, Elsadek MF, Mahmoud SF, Ahmed BM, Khafaga AF. Sidr honey abrogates the oxidative stress and downregulates the hyaluronic acid concentration and gene expression of TGF‐β1 and COL1a1 in rat model of thioacetamide‐induced hepatic fibrosis. Anim Sci J 2020; 91(1): e13434.
  33. Kalmari A, Arash V, Colagar AH. Influence of COL2A1-G1405S polymorphism on mandibular skeletal malocclusions: A genetic association study and in silico analysis. Arch Oral Biol 2022; 142: 105500.
  34. Khoodoruth MAS, Ahammad F, Khan YS, Mohammad F. The shared genetic risk factors between Tourette syndrome and obsessive-compulsive disorder. Frontiers in Neurology 2023; 14: 1283572.
  35. Arai Y, Choi B, Kim BJ, Park S, Park H, Moon JJ, Lee S-H. Cryptic ligand on collagen matrix unveiled by MMP13 accelerates bone tissue regeneration via MMP13/Integrin α3/RUNX2 feedback Acta Biomater 2021; 125: 219-30.
  36. Sánchez K, Maguire-Zeiss K. MMP13 expression is increased following mutant α-synuclein exposure and promotes inflammatory responses in microglia. Front Neurosci 2020; 14: 585544.
Journal of Isfahan Medical School
Volume 43, Issue 813
1st Week, July
July and August 2025
Pages 429-437

  • Receive Date 16 September 2024
  • Accept Date 01 July 2025