The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study

Rui Lai; Bingzun Yin; Ziyang Feng; Xinmin Deng; Xiaofeng Lv; Yumei Zhong; Dezhong Peng

doi:10.3389/fendo.2023.1332383

The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study

Front Endocrinol (Lausanne). 2024 Jan 22:14:1332383. doi: 10.3389/fendo.2023.1332383. eCollection 2023.

Authors

Rui Lai^#¹, Bingzun Yin^#¹, Ziyang Feng^#², Xinmin Deng³, Xiaofeng Lv¹, Yumei Zhong⁴, Dezhong Peng¹

Affiliations

¹ School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China.
³ School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁴ Chengdu Integrated TCM & Western Medicine Hospital/Chengdu First People's Hospital, Chengdu, China.

^# Contributed equally.

Abstract

Objective: Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism.

Method: Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions.

Results: We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1β (MIP-1β) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1β (MIP-1β), stem cell growth factors-β (SCGF-β), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α).

Conclusion: Our study suggests that IL-7 and MIP-1β may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.

Keywords: Mendelian randomization; causal relationship; cytokines; hypothyroidism; inflammatory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemokine CCL4
Cytokines*
Humans
Hypothyroidism* / genetics
Interleukin-7
Mendelian Randomization Analysis

Substances

Cytokines
Chemokine CCL4
Interleukin-7

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Sichuan Provincial Administration of Traditional Chinese Medicine (2021MS090).