Investigating the shared genetic basis and causal relationships between mucosa-associated lymphoid tissue inflammation and psychiatric disorders

Andrea N Georgiou; Konstantinos Voskarides; Panos Zanos; Andreas Chatzittofis

doi:10.3389/fpsyt.2024.1379922

Investigating the shared genetic basis and causal relationships between mucosa-associated lymphoid tissue inflammation and psychiatric disorders

Front Psychiatry. 2024 Apr 29:15:1379922. doi: 10.3389/fpsyt.2024.1379922. eCollection 2024.

Authors

Andrea N Georgiou¹, Konstantinos Voskarides^{2

3}, Panos Zanos¹, Andreas Chatzittofis^{4

5}

Affiliations

¹ Department of Psychology, University of Cyprus, Nicosia, Cyprus.
² Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus.
³ School of Veterinary Medicine, University of Nicosia, Nicosia, Cyprus.
⁴ Medical School, University of Cyprus, Nicosia, Cyprus.
⁵ Department of Clinical Sciences/Psychiatry, Umeå University, Umeå, Sweden.

Abstract

Background: Chronic and acute inflammation of the mucosa-associated lymphoid tissue have been positively linked to the development of psychiatric disorders in observational studies. However, it remains unclear whether this association is causal. In the present study, we investigated this association, using as proxies genetically predicted tonsillectomy, appendectomy and appendicitis on psychiatric disorders including major depressive disorder (MDD), schizophrenia (SCZ), bipolar depression (BD) and anxiety (ANX) via a two-sample Mendelian randomization (MR) analysis.

Methods: Genetic association summary statistics for tonsillectomy, appendectomy and appendicitis were sourced from FinnGen Consortium, comprising data from 342,000 participants. Genetic correlations between all exposures and outcome were calculated with Linkage Disequilibrium Score (LDSC) Regression analysis. MR estimates were then calculated to assess their impact on the risk of developing psychiatric disorders. Sensitivity analysis was employed to test for any directional pleiotropy.

Results: Our results suggest that there is no direct causal association between tonsillectomy, appendectomy or appendicitis with a heightened risk for development of psychiatric disorders. The robustness of the results of the main MR analysis was further confirmed with additional sensitivity analyses. However, a moderate inverse genetic correlation was observed between tonsillectomy and MDD traits (r_g=-0.39, p-value (P)=7.5x10^-5).

Conclusion: Our findings provide, for the first time, evidence that there is no causal association between tonsillectomy or appendectomy on subsequent vulnerability of developing psychiatric disorders. Future studies using larger sample size GWAS should focus on unraveling the confounding factors and mediators to investigate this relationship further.

Keywords: Mendelian randomization; appendectomy; appendicitis; mucosa-associated lymphoid tissue inflammation; psychiatric disorders; tonsillectomy.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.