Causal relationships between autoimmune diseases and celiac disease: A Mendelian randomization analysis

ABSTRACT

The aim of this study was to investigate the causal relationship between autoimmune disorders and celiac disease (CeD) through Mendelian randomization (MR). Single nucleotide polymorphisms (SNPs) significantly associated with 13 autoimmune diseases were extracted from the summary statistics of European genome-wide association studies (GWAS), and their effects were examined by Inverse variance-weighted (IVW) in a large European GWAS on CeD. Finally, reverse MR was performed to investigate the causal effects of CeD on autoimmune traits. Following the application of Bonferroni correction for multiple testing, genetically determined seven autoimmune diseases are causally associated with CeD: Crohn’s disease (CD) (OR [95%CI] = 1.156 [1.106 ± 1.208], P = 1.27E–10), primary biliary cholangitis (PBC) (1.229 [1.143 ± 1.321], P = 2.53E–08), primary sclerosing cholangitis (PSC) (1.688 [1.466 ± 1.944], P = 3.56E–13), rheumatoid arthritis (RA) (1.231 [1.154 ± 1.313], P = 2.74E–10), systemic lupus erythematosus (SLE) (1.127 [1.081 ± 1.176], P = 2.59E–08), type 1 diabetes (T1D) (1.41 [1.238 ± 1.606], P = 2.24E–07), and asthma (1.414 [1.137 ± 1.758], P = 1.86E–03). The IVW analysis indicated that CeD increased the risk for seven diseases: CD (1.078 [1.044 ± 1.113], P = 3.71E–06), Graves’ disease (GD) (1.251 [1.127 ± 1.387], P = 2.34E–05), PSC (1.304 [1.227 ± 1.386], P = 8.56E–18), psoriasis (PsO) (1.12 [1.062 ± 1.182], P = 3.38E–05), SLE (1.301[1.22 ± 1.388], P = 1.25E–15), T1D (1.3[1.228 ± 1.376], P = 1.57E–19), and asthma (1.045 [1.024 ± 1.067], P = 1.82E–05). The sensitivity analyses deemed the results reliable without pleiotropy. There are positive genetic correlations between various autoimmune diseases and CeD, and the latter also affects the predisposition to multiple autoimmune disorders in the European population.

KEYWORDS:

• Mendelian randomization
• celiac disease
• autoimmune diseases
• causal relationship
• GWAS

Acknowledgements

We thank the relevant consortia for sharing the GWAS summary statistics and making their data available.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data sharing agreement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/02648725.2023.2215039

Additional information

Funding

This study was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region (No. 2021D01C200 and No.20200103).

Notes on contributors

Ting Li

Ting Li Ph.D., excels in the diagnosis and treatment of common digestive diseases. Research direction: celiac disease and inflammatory bowel disease.

Yan Feng

Yan Feng Master, excels in the diagnosis and treatment of gastrointestinal diseases such as gastrointestinal early cancer and inflammatory bowel disease. Research direction: Early cancer of the digestive tract and autoimmune gastrointestinal disease.

Chun Wang

Chun Wang is currently working as director of the pathology department of the People’s Hospital of Xinjiang Uygur Autonomous Region. She has extensive research experience in early cancer of the digestive tract and autoimmune gastrointestinal diseases. She is also serving as a reviewer for many international reputed journals. She has participated in multiple international conferences and workshops.

Tian Shi

Tian Shi Ph.D., excels in the diagnosis and treatment of common digestive diseases. Research direction: celiac disease and inflammatory bowel disease.

Xiaoling Huang

Xiaoling Huang The expert has long been engaged in the diagnosis and treatment of various diseases of the digestive tract, such as Kaposi's sarcoma, inflammatory bowel disease.

Mireayi Abuduhadeer

Mireayi Abuduhadeer The expert has long been engaged in the diagnosis and treatment of various diseases of the digestive tract, such as inflammatory bowel disease, etc.

Adilai Abudurexiti

Adilai Abudurexiti Master, excels in the diagnosis and treatment of common digestive diseases. Research direction: celiac disease and inflammatory bowel disease.

Mengxia Zhang

Mengxia Zhang Master, excels in the diagnosis and treatment of common digestive diseases. Research direction: celiac disease and inflammatory bowel disease.

Feng Gao

Feng Gao is currently working as director of the Gastroenterology department of People’s Hospital of Xinjiang Uygur Autonomous Region. He has extensive research experience in celiac disease and autoimmune gastrointestinal diseases. He is also serving as a reviewer for many international reputed journals. He has participated in multiple international conferences and workshops.