Autoimmune diseases and diffuse large B-cell lymphoma: A Mendelian randomization study

自身免疫性疾病与弥漫性大B细胞淋巴瘤:一项孟德尔随机化研究

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Abstract

The causal link between autoimmune diseases (ADs) and diffuse large B-cell lymphoma (DLBCL) remains uncertain. This study aims to assess the causal effects of ADs on DLBCL risk using Mendelian randomization (MR). The summary dataset for ADs and lymphoma genome-wide association study (GWAS) was sourced from the open GWAS website. Single nucleotide polymorphisms were chosen as genetic instrumental variants based on linkage disequilibrium with P < 5 × 10-8 and R2 = 0.01 in different ADs GWAS. Palindrome and outlier single nucleotide polymorphisms were excluded. Cochran Q test, the MR-EGGER intercept test, MR-PRESSO, and leave-one-out analysis were used to assess sensitivity. Our results showed genetic liability to 6 ADs, including mixed connective tissue disease (odds ratios, ORWM1.578; 95% confidence intervals [CI]: 1.250-1.991, P < .001), psoriasis (ORMR-Egger = 0.775; 95% CI: 0.604-0.992, P = .049), Sjögren syndrome (ORIVW = 1.290; 95% CI: 1.072-1.551, P = .007), systemic lupus erythematosus (ORIVW = 1.153; 95% CI: 1.053-1.262, P = .002), type 1 diabetes mellitus (ORIVW = 0.899; 95% CI: 0.862-0.938, P < .001), and ulcerative colitis (ORMR-Egger = 1.648; 95% CI: 1.210-2.243, P = .003) may have a causal relationship with DLBCL. Our MR results showed that ADs, such as Sjögren syndrome and systemic lupus erythematosus, may have causal relationship with DLBCL, while type 1 diabetes mellitus could reduce the risk of DLBCL.

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