Abstract
Obsessive-compulsive disorder (OCD) is a complex multi-gene disorder. In the current study, we genotyped six single nucleotide polymorphisms (SNPs) within MOCOS, NINJ2 and AKT1 genes in a cohort of Iranian patients with this disorder and healthy controls. C allele of rs1057251 has been found to increase risk of OCD (OR (95% CI) =6.39 (4.64-8.79), P value <0.001). This SNP has been associated with risk of OCD in codominant model (OR (95% CI) = 69.53 (25.02-193.21) and 147 (34.2-631.75) for TC and CC genotypes, respectively, P value <0.0001). The rs1057251 was also associated with risk of OCD in dominant (OR (95% CI) = 72.87 (26.28-202.03), P value <0.0001), recessive (OR (95% CI) = 7.43 (2.49-22.19), P value =0.0002), overdominant (OR (95% CI) = 20.2 (11.1-36.76), P value <0.0001) and log-additive (OR (95% CI) = 20.87 (13.83-56.14), P value <0.0001) models. The rs3809263 within NINJ2 was also associated with risk of OCD. The A allele of this SNP has been found to confer risk of OCD (OR (95% CI) =3.28 (2.41-4.48), P value <0.001). This SNP was associated with risk of OCD in codominant (P value <0.0001), dominant (P value <0.0001), overdominant (OR (95% CI) = 9.28 (5.23-16.46), P value<0.0001) and log-additive (OR (95% CI) = 5.25 (3.4-8.1), P value <0.0001) models. Other SNPs were not associated with risk of OCD in any inheritance model. Taken together, rs1057251 and rs3809263 can be considered as risk loci for OCD in Iranian population.
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The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
References
(2013) Diagnostic and statistical manual of mental disorders, Fifth edition. Am Psychiatric Assoc, 21
Araki T, Milbrandt J (2000) Ninjurin2, a novel homophilic adhesion molecule, is expressed in mature sensory and enteric neurons and promotes neurite outgrowth. J Neurosci 20:187–195
Beaulieu J-M, Sotnikova TD, Yao W-D, Kockeritz L, Woodgett JR, Gainetdinov RR, Caron MG (2004) Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proceedings of the National Academy of Sciences 101:5099–5104
Feron F, Gepner B, Lacassagne E, Stephan D, Mesnage B, Blanchard MP, Boulanger N, Tardif C, Deveze A, Rousseau S, Suzuki K, Izpisua Belmonte JC, Khrestchatisky M, Nivet E, Erard-Garcia M (2016) Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders. Mol Psychiatry 21:1215–1224
First MB, Spitzer RL, Gibbon M, Williams JB (1995) Structured clinical interview for DSM-IV axis I disorders-patient edition (SCID-I/P, version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New York, p 722
Ghafouri-Fard S, Azari I, Hashemian F, Nejatizadeh A, Taheri M (2020) No association between AKT1 polymorphisms and methamphetamine addiction in Iranian population. J Mol Neurosci 70:303–307
Kurzawski M, Dziewanowski K, Safranow K, Drozdzik M (2012) Polymorphism of genes involved in purine metabolism (XDH, AOX1, MOCOS) in kidney transplant recipients receiving azathioprine. Ther Drug Monit 34:266–274
Malekzadeh V, Azari I, Noroozi R, Shams R, Farzaneh M, Taheri M, Ghafouri-FARD S (2019) Genetic variants within Ninjurin 2 gene are associated with risk of ischemic stroke in Iranian population. Neurol Sci 40:2603–2607
Micheli V, Camici M, Tozzi GM, Ipata LP, Sestini S, Bertelli M, Pompucci G (2011) Neurological disorders of purine and pyrimidine metabolism. Curr Top Med Chem 11:923–947
Mohammadi MR, Ghanizadeh A, Rahgozar M, Noorbala AA, Davidian H, Afzali HM, Naghavi HR, Yazdi SAB, Saberi SM, Mesgarpour B (2004) Prevalence of obsessive-compulsive disorder in Iran. BMC Psychiatry 4:1–8
O'Connell KS, Mcgregor NW, Lochner C, Emsley R, Warnich L (2018) The genetic architecture of schizophrenia, bipolar disorder, obsessive-compulsive disorder and autism spectrum disorder. Mol Cell Neurosci 88:300–307
Safa A, Omrani MD, Nicknafs F, Oskooei VK, Taheri M, Ghafouri-Fard S (2020) Assessment of association between NINJ2 polymorphisms and suicide attempts in an Iranian population. J Mol Neurosci 70:1880–1886
Sayad A, Ghafouri-Fard S, Omrani MD, Taheri M (2020) Associations between two single-nucleotide polymorphisms in NINJ2 gene and risk of psychiatric disorders. J Mol Neurosci 70:236–245
Simmonds HA, Panayi GS, Corrigall V (1978) A role for purine metabolism in the immune response: adenosine-deaminase activity and deoxyadenosine catabolism. Lancet 1:60–63
Sole X, Guinó E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies. Bioinformatics 22:1928–1929
Taheri M, Noroozi R, Aghaei K, Omrani MD, Ghafouri-Fard S (2020) The rs594445 in MOCOS gene is associated with risk of autism spectrum disorder. Metab Brain Dis 35:497–501
Taylor S (2011) Etiology of obsessions and compulsions: a meta-analysis and narrative review of twin studies. Clin Psychol Rev 31:1361–1372
Taylor S (2013) Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry 18:799–805
Taylor S, Jang KL, Asmundson GJ (2010) Etiology of obsessions and compulsions: a behavioral-genetic analysis. J Abnorm Psychol 119:672
Teixeira AL, Rodrigues DH, Marques AH, Miguel EC, Fontenelle LF (2014) Searching for the immune basis of obsessive-compulsive disorder. Neuroimmunomodulation 21:152–158
Wang Q, Liu L, Pei L, Ju W, Ahmadian G, Lu J, Wang Y, Liu F, Wang YT (2003) Control of synaptic strength, a novel function of Akt. Neuron 38:915–928
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This study was financially supported by Shahid Beheshti University of Medical Sciences (Grant number 27999).
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EB, BMH and MT performed the experiment. VKO analyzed the data. SGF and SMN designed the study and wrote the draft and revised it. All the authors contribute equally and read the submission.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent forms were obtained from all study participants. The study protocol was approved by the ethical committee of Shahid Beheshti University of Medical Sciences. All methods were performed in accordance with the relevant guidelines and regulations.
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Taheri, M., Badrlou, E., Hussen, B.M. et al. Association between genetic variants and risk of obsessive-compulsive disorder. Metab Brain Dis 37, 525–530 (2022). https://doi.org/10.1007/s11011-021-00870-w
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DOI: https://doi.org/10.1007/s11011-021-00870-w