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Association of OXTR polymorphism (rs53576) with depression: a meta-analysis

Egyptian Journal of Medical Human Genetics volume 24, Article number: 75 (2023) Cite this article

Abstract

Background

Depression is a common psychiatric disorder that negatively affects mood and thoughts. Association studies of OXTR polymorphisms with depression have been performed repeatedly. However, the results of these studies were inconsistent. The aim of the present study was to perform a meta-analysis of case–control studies that have investigated the relationship between the OXTR polymorphism (rs53576) and depression risk.

Methods

Four databases, PubMed, ScienceDirect, Springer Link, and Google Scholar, were searched, and a total of 10 studies were involved in the meta-analysis. ReviewManager (RevMan) 5.4 software was used to perform a meta-analysis of the eligible studies.

Results

A significant association between OXTR rs53576 and depression was found in the recessive model (Odds Ratio (OR) AA vs. AG + GG = 1.28, 95% Confidence Interval (CI) [1.02–1.59], P = 0.03), while there was no association with the other two genetic models (dominant model: OR AA + AG vs. GG = 1.01, 95% CI [0.87–1.18], P = 0.87; allelic model: OR A vs. G = 0.95, 95% CI [0.83–1.09], P = 0.46). A significant association was observed in the Caucasian populations (OR 1.29, 95% CI [1.01, 1.64], P = 0.04), while the Asian populations showed no significant association (OR 1.22, 95% CI [0.71, 2.09], P = 0.48).

Conclusions

This meta-analysis is to date the first to provide a comprehensive investigation of the association of the OXTR rs53576 polymorphism with depression, and its results reflect the data currently available from the literature and can serve as a guide for further research.

Background

Depression is a common mental disorder and a leading cause of disability. According to World Health Organization (WHO), about 1 billion people have mental disorders and over 300 million people suffer from depression worldwide [3]. In the first year of the COVID-19 epidemic, the prevalence of anxiety increased by 25%. Depressive psychopathology was identified in around 35% of patients following infection with the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) [27]. Scientists suggested that the significant increase could be a result of many factors, including fear of infection, financial worries, and social isolation during the pandemic.

Depression is assumed to be caused by the interplay of hereditary and external factors [15, 35]. Genetic factors have been frequently reported to play a significant role in the development of depression [1, 26].

Several genes' potential roles in the development of depression have been assessed in recent years. The most studied genes were oxytocin OXT and oxytocin receptor gene OXTR.

Oxytocin is a neuropeptide produced by the hypothalamus and well-known as a key regulator of human behavior and psychology. The role of oxytocin in social integration, aggression, and antisocial behavior, has been the subject of several studies in recent years [6]. Oxytocin exerts its effects via the oxytocin receptor (OXTR) [21].

OXTR is a G-protein-coupled receptor (GPCR), mostly expressed in the brain but also present in other body tissues, and has been proven to be involved in the development of social skills [38]. This prompted researchers to examine the OXTR gene as a prospective candidate for depression susceptibility.

The OXTR single nucleotide polymorphisms (SNPs) have been associated with human mental health issues [5]. The most studied SNP of OXTR so far is (rs53576) (G/A) in the third intron [19]. This polymorphism has been considered to be associated with human social and emotional behavior due to its potential modulatory effect on oxytocin-dopamine interactions [8]. Studying the influence of OXTR rs53576 on general behavior has been the subject of several studies to evaluate its role as a possible genetic marker for psychiatric disorders [24].

The aim of this study was to perform a meta-analysis of case–control studies that have investigated the association between the OXTR polymorphism (rs53576) and depression risk. Furthermore, subgroup analysis based on ethnicity was conducted to evaluate the association of this polymorphism with depression in Caucasian and Asian populations.

Methods

Study strategies

Meta-analysis was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [28]. Four databases (PubMed, ScienceDirect, Springer Link, and Google Scholar) were searched for case–control studies published in English up to January 2021 that investigated the association of OXTR rs53576 with depression risk in humans. The following keywords were used in the systematic search (“OXTR or oxytocin receptor”, “Polymorphism or genetic variations”, “rs53576”, and “depression”).

Inclusion and exclusion criteria

Included studies had to meet the following criteria: 1) Published case–control studies involving human subjects; 2) Availability of data to calculate Odds Ratio (OR) with confidence interval (CI); and 3) Study the association between OXTR (rs53576) polymorphism and depression.

Exclusion criteria: 1) Reviews, meta-analyses, animal studies, duplication; 2) Irrelevant studies (investigated other diseases or other polymorphisms); and 3) Studies without sufficient information (genotype frequencies, controls).

Data extraction

For each included study, the following data were extracted: 1) First author’s surname 2) Year of publication 3) Country of origin 4) Sample size (case / control) 5) Genotyping data for cases and controls.

Assessment of quality of included studies

The quality of the included studies was evaluated using the Newcastle–Ottawa Quality Assessment Form for Case–Control Studies. The results of the quality evaluation were considerable, with a minimum score of 8, which indicates the high quality of included studies.

Statistical analysis

RevMan 5.4 (Cochrane Collaboration, London, UK) software was used to perform a meta-analysis of the eligible studies. The association between the OXTR (rs53576) polymorphism and depression risk was evaluated by OR with 95% CI in accordance with dominant and recessive inheritance models. Significant difference was considered when P < 0.05. Heterogeneity between studies was evaluated by a chi2-based Cochran Q test and quantified with the I2 statistic (P < 0.05 or I2 > 50% indicated significant heterogeneity). For lower heterogeneity values, Fixed-effect model was used to calculate ORs and 95% CIs. Subgroup analysis was conducted on ethnicity of Caucasian and Asian populations. A sensitivity analysis was performed by sequentially excluding one study at a time. Publication bias was investigated using Begg’s funnel plots.

Results

Characteristics of included studies

The flow chart of studies’ selection and the reasons for exclusion are presented in Fig. 1. 162 articles were identified through database searching based on the keywords, 136 of these were excluded for the following reasons: 27 irrelevant articles, 38 duplicates, 24 reviews, 16 meta-analyses, 28 cohort studies, and 3 animal studies. The 26 remaining articles were assessed for eligibility. Of these, 16 articles were excluded for lack of sufficient information. A total of 10 eligible articles were included in the meta-analysis. An article studied two types of depression, and both types were considered separately.

Fig. 1
figure 1

PRISMA Flow chart of study selection

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The included studies were carried out in the Netherlands [33, 34], Republic of Korea [29], Poland [40], USA [4], Italy [11, 12], Australia [36], Canada [7], and Malaysia [23].

In all 10 included studies, total cases were 1847 and controls were 3673. The main characteristics of the included studies are shown in Table 1.

Table 1 Main characteristics of included studies in meta-analysis
Full size table

Meta-analysis

The main results of meta-analysis and the heterogeneity test are presented in Table 2.

Table 2 The association between OXTR polymorphism (rs53576) and depression risk
Full size table

According to the meta-analysis results, OXTR polymorphism (rs53576) has no significant association with depression in both allelic (Table 2, Fig. 2a) and dominant (Table 2, Fig. 2b) models.

Fig. 2
figure 2

Forest plot of the association between OXTR polymorphism (rs53576) and depression risk in different models: a Allelic, b Dominant, c Recessive

Full size image

The recessive model, on the other hand, shows significant association with the depression risk (Table 2, Fig. 2c) in both fixed effect (OR 1.28, 95% CI [1.02–1.59], P = 0.03) and random effect (OR 1.29, 95% CI [1.04–1.60], P = 0.02) models.

There is no significant heterogeneity in the studied models (Dominant: I2 = 44%, p = 0.06, Recessive: I2 = 0%, p = 0.96, Allelic: I2 = 37%, p = 0.13) (Table 2).

Begg’s funnel plot was used to estimate the publication bias of the included articles. The funnel plots of all the studied models do not show evidence of publication bias (Fig. 3).

Fig. 3
figure 3

Funnel plot of the association between OXTR polymorphism (rs53576) and depression risk in different models: a Allelic, b Dominant, c Recessive

Full size image

Subgroup analysis

In all 9 included studies in the recessive model, 7 studies were from Caucasian and 2 studies were from Asian populations. A significant association between OXTR polymorphism (rs53576) and depression risk is observed in the Caucasian populations (OR = 1.29, 95% CI [1.01, 1.64], p = 0.04) (Fig. 4a), while the Asian populations show no significant association (OR = 1.22, 95% CI [0.71, 2.09], p = 0.48) (Fig. 4b).

Fig. 4
figure 4

Forest plot of the association between OXTR polymorphism (rs53576) and depression risk in different populations: a Caucasian, b Asian

Full size image

Discussion

The association between OXTR gene polymorphisms and the various aspects of human disorders has gained increased interest since the discovery of OXTR gene structure [19]. These studies have evaluated the effect of OXTR gene variations on early childhood behavior, autism spectrum disorder (ASD), depression, anxiety, alcohol abuse, attention deficit hyperactivity disorder (ADHD), borderline personality disorder, and other social and emotional traits [22]. The OXTR SNP rs53576 (G/A) has been associated with the risk of comorbid depressive and disruptive behavior disorders [2]. The association between OXTR SNPs and alcohol abuse was evaluated [10]. OXTR rs53576 had no association with the consumption of alcohol in females, while the male A allele carriers proved to be frequent consumers [37]. The same SNP showed an interaction with childhood maltreatment in the prediction of borderline personality disorder (BPD) [9]. Hovey and colleagues showed that OXTR SNPs rs7632287 and rs4564970 are significantly associated with antisocial behavior in boys [18]. Several studies have examined the association between OXTR polymorphisms and autism spectrum disorder (ASD) and identified differences in the OXTR genotype between ASD cases and controls [22]. The association between OXTR SNPs and ADHD phenotypes was identified among children with ADHD [30]. Also, various studies have directly linked the OXTR SNPs with social abilities and behavior [16].

Previous meta-analyses have examined the role of OXTR polymorphisms in some of the above-mentioned diseases. For example, a meta-analysis was performed to evaluate the association of OXTR polymorphisms with antisocial behavior [31]. Another analysis studied the impact of OXTR rs53576 on empathy [14]. In addition, Li and colleagues performed a meta-analysis and found a positive association between OXTR rs53576 and general sociality [24].

In the current meta-analysis, we used data from 10 studies, including 1847 cases and 3673 controls, and found a significant association of OXTR SNP rs53576 (G/A) with depression in the recessive model, with no association in dominant or allelic models. This suggests that the existence of one (A) allele is not enough to alter the depression risk. According to the meta-analysis results, only people with homozygote genotype (AA) are more susceptible to developing depressive symptoms in their lives. This result is consistent with the findings of the previous studies that have shown associations between the SNP rs53576 and psychological traits, with most of them concluding that (A) allele carriers have an increased sensitivity to stress and negative mental health issues compared to the carriers of the homozygote GG genotype [32].

We also performed a subgroup analysis based on ethnicity and showed a significant association between the studied polymorphism and depression risk in the Caucasian population. However, the Asian subgroup has shown no such association. At this point, we should mention that the rs53576 allele frequencies significantly differ among ethnic groups. (A) allele is a minor allele for Europeans, while it's the opposite for East Asians. This indicates the importance of ethnic homogeneity regarding this polymorphism [40].

This meta-analysis had several strengths. To the best of our knowledge, this meta-analysis is the first to examine the association of OXTR SNP rs53576 with depression risk and to evaluate its impact in different ethnic subgroups. In addition, there was no significant heterogeneity in all the used models (P > 0.05). Moreover, the clear inclusion and exclusion criteria presented in this study strictly ensured the relevance of the included articles and therefore reduced selection bias.

However, several limitations should be mentioned. The number of included studies is considered relatively low, which means that the obtained results reflect the current available data from the literature and can serve as a guide for further research without necessarily providing definitive facts about the impact of the studied SNP. Furthermore, the authors of some of the included articles had conducted their research on a small sample size [7, 29], and having a proper sample size is crucial to avoiding false negative results [17]. In addition, the mechanisms related to oxytocin are sex-dependent [13] and the proportion between males and females should be balanced.

Recently emerging data indicates that the COVID-19 outbreak caused a global significant increase in the prevalence of mental health disorders, including depression and anxiety, due to the governmental implemented measures of self-isolation and social distancing [20, 25]. Scientists suggested that oxytocin could be a strong candidate to relieve social stress amid the pandemic, based on its role in promoting homeostasis, suppressing inflammation, and accelerating damage repair [39]. This draws attention to the importance of studying the association of OXTR SNPs with other diseases, such as COVID-19 and other infections’ severity, besides focusing solely on their impact on the psychological disorders.

Conclusion

The performed meta-analysis indicated an overall association of OXTR SNP rs53576 with increased depression risk in the recessive model of inheritance. Further subgroup analysis confirmed this association in Caucasians, while it was not significant in Asian populations. This suggests that the studied polymorphism has an ethnicity-dependent effect. Considering the diversity of the included studies in terms of sample size, gender balance, and ethnicity, further research is needed to better understand the effect of OXTR rs53576 on depression risk.

Availability of data and materials

Authors confirm that the data supporting the study findings are available within the article.

Abbreviations

OR:

Odds ratio

CI:

Confidence interval

SNP:

Single nucleotide polymorphism

OXT:

Oxytocin

OXTR:

Oxytocin receptor

GPCR:

G-protein coupled receptor

MDD:

Major depressive disorder

ASD:

Autism spectrum disorder

ADHD:

Attention deficit hyperactivity disorder

References

  1. aan het Rot M, Mathew SJ, Charney DS (2009) Neurobiological mechanisms in major depressive disorder. CMAJ 180:305–313

    Article  PubMed  PubMed Central  Google Scholar 

  2. Adrian M, Kiff C, Glazner C, Kohen R, Tracy JH, Zhou C, Vander Stoep A (2015) Examining gene-environment interactions in comorbid depressive and disruptive behavior disorders using a Bayesian approach. J Psychiatr Res 68:125–133

    Article  PubMed  PubMed Central  Google Scholar 

  3. Aleem S, Huda N, Amin R, Khalid S, Alshamrani SS, Alshehri A (2022) Machine learning algorithms for depression: diagnosis, insights, and research directions. Electronics 11(7):1111. https://doi.org/10.3390/electronics11071111

    Article  Google Scholar 

  4. Bell AF, Carter CS, Steer CD et al (2015) Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy. Front Genet 6:243. https://doi.org/10.3389/fgene.2015.00243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Burmester V, Nicholls D, Buckle A, Stanojevic B, Crous-Bou M (2021) Review of eating disorders and oxytocin receptor polymorphisms. J Eat Disord 9(1):85. https://doi.org/10.1186/s40337-021-00438-0

    Article  PubMed  PubMed Central  Google Scholar 

  6. Butovskaya M, Rostovtseva V, Butovskaya P, Burkova V, Dronova D, Filatova V, Sukhodolskaya E, Vasiliev V, Mesa T, Rosa A, Lazebny O (2020) Oxytocin receptor gene polymorphism (rs53576) and digit ratio associates with aggression: comparison in seven ethnic groups. J Physiol Anthropol 39(1):20. https://doi.org/10.1186/s40101-020-00232-y

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chagnon YC, Potvin O, Hudon C, Préville M (2015) DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women. Front Genet 6:230. https://doi.org/10.3389/fgene.2015.00230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chang WH, Lee IH, Chen KC, Chi MH, Chiu NT, Yao WJ, Lu RB, Yang YK, Chen PS (2014) Oxytocin receptor gene rs53576 polymorphism modulates oxytocin-dopamine interaction and neuroticism traits–a SPECT study. Psychoneuroendocrinology 47:212–220. https://doi.org/10.1016/j.psyneuen.2014.05.020

    Article  CAS  PubMed  Google Scholar 

  9. Cicchetti D, Rogosch FA, Hecht KF, Crick NR, Hetzel S (2014) Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes. Dev Psychopathol 26(3):831–849

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cleveland HH, Griffin AM, Wolf PSA, Wiebe RP, Schlomer GL, Feinberg ME, Vandenbergh DJ (2018) Transactions between substance use intervention, the oxytocin receptor (OXTR) gene, and peer substance use predicting youth alcohol use. Prev Sci 19(1):15–26

    Article  PubMed  PubMed Central  Google Scholar 

  11. Costa B, Pini S, Baldwin DS et al (2017) Oxytocin receptor and G-protein polymorphisms in patients with depression and separation anxiety. J Affect Disord 218:365–373. https://doi.org/10.1016/j.jad.2017.03.056

    Article  CAS  PubMed  Google Scholar 

  12. Costa B, Pini S, Gabelloni P et al (2009) Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology 34(10):1506–1514. https://doi.org/10.1016/j.psyneuen.2009.05.006

    Article  CAS  PubMed  Google Scholar 

  13. Dumais KM, Veenema AH (2015) Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior. Front Neuroendocrinol. https://doi.org/10.1016/j.yfrne.2015.04.003

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gong P, Fan H, Liu J, Yang X, Zhang K, Zhou X (2017) Revisiting the impact of OXTR rs53576 on empathy: a population-based study and a meta-analysis. Psychoneuroendocrinology 80:131–136. https://doi.org/10.1016/j.psyneuen.2017.03.005

    Article  CAS  PubMed  Google Scholar 

  15. Grippo AJ, Gerena D, Huang J, Kumar N, Shah M, Ughreja R, Carter CS (2007) Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles. Psychoneuroendocrinology 32:966–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. He J, Buil JM, Koot HM, van Lier PAC (2018) Associations between Oxytocin receptor (OXTR) genotype and elementary school children’s likability, dis-likability and friendship among classroom peers: a longitudinal study. J Youth Adolesc 47(9):1799–1812

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hong EP, Park JW (2012) Sample size and statistical power calculation in genetic association studies. Genomics Inform 10:117–122

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hovey D, Lindstedt M, Zettergren A, Jonsson L, Johansson A, Melke J, Westberg L (2016) Antisocial behavior and polymorphisms in the oxytocin receptor gene: findings in two independent samples. Mol Psychiatry 21(7):983–988

    Article  CAS  PubMed  Google Scholar 

  19. Inoue T, Kimura T, Azuma C, Inazawa J, Takemura M, Kikuchi T et al (1994) Structural organization of the human oxytocin receptor gene. J Biol Chem 269:32451–32456

    Article  CAS  PubMed  Google Scholar 

  20. Kantor BN, Kantor J (2020) Mental health outcomes and associations during the COVID-19 pandemic: a cross-sectional population-based study in the United States. Front Psychiatry 11:569083. https://doi.org/10.3389/fpsyt.2020.569083

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H (1992) Structure and expression of a human oxytocin receptor. Nature 356(6369):526–529

    Article  CAS  PubMed  Google Scholar 

  22. Kohlhoff J, Cibralic S, Hawes DJ, Eapen V (2022) Oxytocin receptor gene (OXTR) polymorphisms and social, emotional and behavioral functioning in children and adolescents: a systematic narrative review. Neurosci Biobehav Rev 135:104573. https://doi.org/10.1016/j.neubiorev.2022.104573

    Article  CAS  PubMed  Google Scholar 

  23. Lee KW, Ching SM, Ramachandran V et al (2019) Association analysis of 14 candidate gene polymorphism with depression and stress among gestational diabetes mellitus. Genes (Basel) 10(12):988. https://doi.org/10.3390/genes10120988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li J, Zhao Y, Li R, Broster LS, Zhou C, Yang S (2015) Association of oxytocin receptor gene (OXTR) rs53576 polymorphism with sociality: a meta-analysis. PLoS ONE 10(6):e0131820. https://doi.org/10.1371/journal.pone.0131820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu CH, Zhang E, Wong GTF, Hyun S, Hahm HC (2020) Factors associated with depression, anxiety, and PTSD symptomatology during the COVID-19 pandemic: clinical implications for U.S. young adult mental health. Psychiatry Res 290:113172. https://doi.org/10.1016/j.psychres.2020.113172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Martinowich K, Schloesser RJ, Manji HK (2009) Bipolar disorder: from genes to behavior pathways. J Clin Invest 119:726–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mazza MG, Palladini M, Poletti S et al (2022) Post-COVID-19 depressive symptoms: epidemiology, pathophysiology, and pharmacological treatment. CNS Drugs 36:681–702. https://doi.org/10.1007/s40263-022-00931-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  29. Na KS, Won E, Kang J et al (2018) Interaction effects of oxytocin receptor gene polymorphism and depression on hippocampal volume. Psychiatry Res Neuroimaging 282:18–23. https://doi.org/10.1016/j.pscychresns.2018.10.004

    Article  PubMed  Google Scholar 

  30. Park J, Willmott M, Vetuz G, Toye C, Kirley A, Hawi Z, Kent L (2010) Evidence that genetic variation in the oxytocin receptor (OXTR) gene influences social cognition in ADHD. Prog NeuroPsychopharmacol Biol Psychiatry 34(4):697–702

    Article  CAS  PubMed  Google Scholar 

  31. Poore HE, Waldman ID (2020) The association of oxytocin receptor gene (OXTR) polymorphisms with antisocial behavior: a meta-analysis. Behav Genet 50(3):161–173. https://doi.org/10.1007/s10519-020-09996-6

    Article  PubMed  Google Scholar 

  32. Saphire-Bernstein S, Way BM, Kim HS, Sherman DK, Taylor SE (2011) Oxytocin receptor gene (OXTR) is related to psychological resources. Proc Natl Acad Sci U S A 108(37):15118–15122. https://doi.org/10.1073/pnas.1113137108

    Article  PubMed  PubMed Central  Google Scholar 

  33. Smarius LJCA, Strieder TGA, Doreleijers TAH, Vrijkotte TGM, Zafarmand MH, de Rooij SR (2019) Common oxytocin polymorphisms interact with maternal verbal aggression in early infancy impacting blood pressure at age 5–6: the ABCD study. PLoS One 14(6):e0216035. https://doi.org/10.1371/journal.pone.0216035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Smarius LJCA, Strieder TGA, Doreleijers TAH, Vrijkotte TGM, Zafarmand MH, de Rooij SR (2020) Maternal verbal aggression in early infancy and child’s internalizing symptoms: interaction by common oxytocin polymorphisms. Eur Arch Psychiatry Clin Neurosci 270(5):541–551. https://doi.org/10.1007/s00406-019-01013-0

    Article  PubMed  Google Scholar 

  35. Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4:141–194

    Article  CAS  PubMed  Google Scholar 

  36. Thompson SM, Hammen C, Starr LR, Najman JM (2014) Oxytocin receptor gene polymorphism (rs53576) moderates the intergenerational transmission of depression. Psychoneuroendocrinology 43:11–19. https://doi.org/10.1016/j.psyneuen.2014.01.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Vaht M, Kurrikoff T, Laas K, Veidebaum T, Harro J (2016) Oxytocin receptor gene variation rs53576 and alcohol abuse in a longitudinal population representative study. Psychoneuroendocrinology 74:333–341

    Article  CAS  PubMed  Google Scholar 

  38. Vaidyanathan R, Hammock EAD (2016) Oxytocin receptor dynamics in the brain across development and species. Dev Neurobiol 77(2):143–157

    Article  PubMed  Google Scholar 

  39. Wang SC, Zhang F, Zhu H et al (2022) Potential of endogenous oxytocin in endocrine treatment and prevention of COVID-19. Front Endocrinol (Lausanne) 13:799521. https://doi.org/10.3389/fendo.2022.799521

    Article  PubMed  Google Scholar 

  40. Wasilewska K, Pawlak A, Kostrzewa G et al (2017) OXTR polymorphism in depression and completed suicide-a study on a large population sample. Psychoneuroendocrinology 77:84–89. https://doi.org/10.1016/j.psyneuen.2016.12.003

    Article  CAS  PubMed  Google Scholar 

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  1. Southern Federal University, Ave. Stachki 194/1, Rostov‑on‑Don, Russian Federation, 344090

    Moez Eid, Ekaterina G. Derevyanchuk & Elena V. Butenko

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Contributions

ME: Study design. ME, ED, and EB: Search for articles, data extraction from the included studies, and performing meta-analysis. ME: Writing- original draft. ED and EB: Writing-review and editing. All authors read and approved the final manuscript.

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Correspondence to Moez Eid.

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Eid, M., Derevyanchuk, E.G. & Butenko, E.V. Association of OXTR polymorphism (rs53576) with depression: a meta-analysis. Egypt J Med Hum Genet 24, 75 (2023). https://doi.org/10.1186/s43042-023-00454-6

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