Autoimmune diseases and COPD risk: A Mendelian randomization study.
Studies in epidemiology have indicated a link between chronic obstructive pulmonary disease (COPD) and various autoimmune conditions.This study aimed to investigate the potential causal link between nine autoimmune diseases with a genetic basis and COPD using a two-sample Mendelian randomization (MR) analysis.
To test the impact of susceptibility to immune-related outcomes on genetic prediction of COPD risk, we used pooled statistics from the largest genome-wide association study (GWAS) in Europe in a two-sample MR setting.Genetic data for type 1 diabetes, hypothyroidism, systemic lupus erythematosus, and primary biliary cirrhosis were obtained from the European Bioinformatics Institute (EBI), while data for multiple sclerosis and primary sclerosing cholangitis were extracted from the Integrative Epidemiology Unit (IEU) database. Additionally, genetic data for ulcerative colitis, rheumatoid arthritis, and celiac disease were also collected.These nine autoimmune diseases and the COPD cohort from the UK Biobank (1605 cases and 461,328 controls) were analyzed separately as exposure and outcome.Our primary method for the initial screening was inverse variance weighting (IVW).The MR-Egger regression test assessed multivariate validity, while the Cochran's Q test examined heterogeneity.To ensure the reliability of the findings, a leave-one-out analysis was conducted.
IVW discovered proof of type 1 diabetes (OR = 1.0003; 95 % CI = 1.0000-1.0005; P = 0.046), hypothyroidism (OR = 1.0004; 95 % CI = 1.0001-1.0008; P = 0.0263), celiac disease (OR = 1.0002; 95 % CI = 1.0000-1.0004; P = 0.0168) and systemic lupus erythematosus (OR = 1.0002; 95 % CI = 1.0000-1.0004; P = 0.049) were significantly linked to the heightened risk of COPD with no signs of variation or pleiotropy.Even after accounting for potential confounding factors like smoking, the correlation remained robust.Additionally, our research found that the IVW method did not indicate any causal link between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis (all P >0.05).
This research discovered that individuals with type 1 diabetes, hypothyroidism, celiac disease, and systemic lupus erythematosus have a higher likelihood of developing COPD.Additionally, this research revealed no connection between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis.
Ma X
，Sun Y
，Mou H
，Zhang W
... -
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Investigation of the causal association between Parkinson's disease and autoimmune disorders: a bidirectional Mendelian randomization study.
To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk.
By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results.
Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; P = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; P = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility.
In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments in vitro and in vivo, are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.
Yang J
，Lin W
，Ma Y
，Song H
，Mu C
，Wu Q
，Han C
，Zhang J
，Liu X
... -
《Frontiers in Immunology》
Genetic link between rheumatoid arthritis and autoimmune liver diseases: A two-sample Mendelian randomization study.
An association between rheumatoid arthritis (RA) and autoimmune liver diseases (AILDs) was found in observational studies. However, neither the direction nor the cause-effect chain was clear. This study aimed to assess the causal associations between AILDs and RA.
We performed a two-sample Mendelian randomization (MR) analysis. Following a strict assessment, genome-wide association study (GWAS) datasets were used to select potential candidate single-nucleotide polymorphisms. The inverse-variance weighted (IVW) was used as the primary analysis approach, supplemented with four sensitive analysis methods applied to assess the robustness of the results.
We discovered that a genetically increased primary biliary cholangitis (PBC) risk had a positive causal effect on RA (IVW OR=1.149, 95% CI=1.063-1.241, P<0.001). According to the MR-Egger regression, horizontal pleiotropy was unlikely to impact causality (intercept = -0.028, P = 0.263). Using the leave-one-out strategy, sensitivity studies revealed that the MR analysis results were robust and reliable. Genetically determined primary sclerosing cholangitis (PSC) was not linked with the risk of RA (IVW OR=1.071, 95%CI=0.984-1.166, P = 0.111). The results of the MR analysis were further validated by sensitivity analyses utilizing the leave-one-out approach. In the other direction, there was no causal relationship between RA and PBC (OR=1.132, 95% CI=0.881-1.454, P = 0.333) or PSC (OR=1.067, 95% CI=0.891-1.279, P = 0.088).
Using a two-sample MR analysis, we investigated the relationship between AILDs and RA and revealed first that PBC increases the risk of RA. Large-scale cross-disease GWAS are required to further illuminate the genomic landscape of AILDs and RA.
Fan J
，Jiang T
，He D
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ResearchGate
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