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

Abstract

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.