Large-scale genome-wide association study to identify causal relationships and potential mediators between education and autoimmune diseases

Yingjie Li; Jingwei Zhang; Jie Wen; Mingren Liu; Wanyao Liu; Yongzhen Li

doi:10.3389/fimmu.2023.1249017

Large-scale genome-wide association study to identify causal relationships and potential mediators between education and autoimmune diseases

Front Immunol. 2023 Dec 7:14:1249017. doi: 10.3389/fimmu.2023.1249017. eCollection 2023.

Authors

Yingjie Li^#^{1

2}, Jingwei Zhang^#^{3

4

5}, Jie Wen^{3

4

5}, Mingren Liu^{3

4

5}, Wanyao Liu⁶, Yongzhen Li⁷

Affiliations

¹ Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, China.
² The Institution of Hepatology, Central South University, Changsha, China.
³ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
⁴ Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, Changsha, China.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁶ Xiangya School of Medicine, Central South University, Changsha, China.
⁷ Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, China.

^# Contributed equally.

Abstract

Objectives: Epidemiological studies suggested a potential connection between education and autoimmune disorders. This study investigated the possible cause-and-effect relationship using a Mendelian randomization approach.

Methods: We explored the causality between four education traits (n = 257,841~1,131,881) and 22 autoimmune diseases. The mediating role of smoking (632,802 individuals), BMI (681,275 individuals), alcohol (335,394 individuals), and income (397,751 individuals) was also investigated. Transcriptome-wide association study (TWAS) and enriched signaling pathways analysis were used to investigate the underlying biological mechanisms.

Results: Especially, higher cognitive performance was protective for psoriasis (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.60-0.79, p = 6.12×10^-8), rheumatoid arthritis (RA) (OR = 0.75, 95% CI = 0.67-0.83, p = 4.62×10^-6), and hypothyroidism (OR = 0.83, 95% CI = 0.77-0.90, p = 9.82×10^-6). Higher levels of educational attainment decreased risks of psoriasis (OR = 0.61, 95% CI = 0.52-0.72, p = 1.12×10^-9), RA (OR = 0.68, 95% CI = 0.59-0.79, p = 1.56×10^-7), and hypothyroidism (OR = 0.80, 95% CI = 0.72-0.88, p = 5.00×10^-6). The completion of highest-level math class genetically downregulates the incidence of psoriasis (OR = 0.66, 95% CI = 0.58-0.76, p = 2.47×10^-9), RA (OR = 0.71, 95% CI = 0.63-0.81, p = 5.28×10^-8), and hypothyroidism (OR = 0.85, 95% CI = 0.79-0.92, p = 8.88×10^-5). Higher self-reported math ability showed protective effects on Crohn's disease (CD) (OR = 0.67, 95% CI = 0.55-0.81, p = 4.96×10^-5), RA (OR = 0.76, 95% CI = 0.67-0.87, p = 5.21×10^-5), and psoriasis (OR = 0.76, 95% CI = 0.65-0.88, p = 4.08×10^-4). Protein modification and localization, response to arsenic-containing substances may participate in the genetic association of cognitive performance on UC, RA, psoriasis, and hypothyroidism. According to mediation analyses, BMI, smoking, and income served as significant mediators in the causal connection between educational traits and autoimmune diseases.

Conclusion: Higher levels of education-related factors have a protective effect on the risk of several autoimmune disorders. Reducing smoking and BMI and promoting income equality can mitigate health risks associated with low education levels.

Keywords: Mendelian randomization; Transcriptome-wide association study; autoimmune diseases; causal relationship; education.

Publication types

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

MeSH terms

Arthritis, Rheumatoid* / epidemiology
Arthritis, Rheumatoid* / genetics
Autoimmune Diseases* / epidemiology
Autoimmune Diseases* / genetics
Educational Status
Genome-Wide Association Study
Humans
Hypothyroidism* / epidemiology
Hypothyroidism* / genetics
Mendelian Randomization Analysis
Psoriasis* / epidemiology
Psoriasis* / genetics

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 the Hunan Provincial Health Committee Foundation of China (no. B202306017169) and Changsha Natural Science Foundation (kq2208314).