Dataset Information

Influence of genetically predicted autoimmune diseases on NAFLD.

ABSTRACT:

Introduction

Non-alcoholic fatty liver disease (NAFLD), the emerging cause of end-stage liver disease, is the most common liver disease. Determining the independent risk factors of NAFLD and patients who need more monitoring is important.

Methods

Two-Sample Mendelian randomization (MR) was performed in the analysis to investigate the causal association of different autoimmune diseases with NAFLD using summary level data. Genome-wide association study (GWAS) of 5 autoimmune diseases including celiac disease (CeD), Crohn's disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and type 1 diabetes (T1D) were selected for Instrument variables (IVs). NAFLD was included as outcome.

Result

After adjusting for confounding factors, genetic predisposition of CeD (OR= 0.973, [0.949,0.997], IVW p-value=0.026), MS (OR= 1.048, [1.012,1.085], IVW p-value= 0.008), RA (OR= 1.036, [1.006,1.066], IVW p-value=0.019), T1D (OR= 1.039, [1.002,1.079], IVW p-value= 0.041) is causally associated with NAFLD. No causal effect was found between CD and NAFLD.

Conclusion

CeD itself may be a protective factor for NAFLD, the results of previous observational studies have been influenced by confounding factors, and the morbidity of NAFLD may be higher in patients with MS, RA, and T1D than in common populations, and monitoring the prevalence of NAFLD in these populations is considerable.

SUBMITTER: Xu M

PROVIDER: S-EPMC10520707 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Influence of genetically predicted autoimmune diseases on NAFLD.

Xu Min M Wu Tong T Li Zhaoxia Z Xin Guijie G

Frontiers in immunology 20230911

<h4>Introduction</h4>Non-alcoholic fatty liver disease (NAFLD), the emerging cause of end-stage liver disease, is the most common liver disease. Determining the independent risk factors of NAFLD and patients who need more monitoring is important.<h4>Methods</h4>Two-Sample Mendelian randomization (MR) was performed in the analysis to investigate the causal association of different autoimmune diseases with NAFLD using summary level data. Genome-wide association study (GWAS) of 5 autoimmune disease ...[more]

PMID: 37767101

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Project description:Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers. Univariate MiXeR was used to contrast the genetic architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) was performed using independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted and weighted median MR estimates were evaluated. Sensitivity analyses for uncorrelated (MR PRESSO) and correlated horizontal pleiotropy (CAUSE) were also performed. PTSD was considerably more polygenic (10,863 influential variants) than autoimmune diseases (median 255 influential variants). However, PTSD evidenced significant genetic correlation with nine autoimmune diseases and three inflammatory biomarkers. PTSD had putative causal effects on autoimmune thyroid disease (p = 0.00009) and C-reactive protein (CRP) (p = 4.3 × 10-7). Inferences were not substantially altered by sensitivity analyses. Additionally, the PTSD-autoimmune thyroid disease association remained significant in multivariable MR analysis adjusted for genetically predicted inflammatory biomarkers as potential mechanistic pathway variables. No autoimmune disease had a significant causal effect on PTSD (all p values > 0.05). Although causal effect models were supported for associations of PTSD with CRP, shared pleiotropy was adequate to explain a putative causal effect of CRP on PTSD (p = 0.18). In summary, our results suggest a significant genetic overlap between PTSD, autoimmune diseases, and biomarkers of inflammation. PTSD has a putative causal effect on autoimmune thyroid disease, consistent with existing epidemiologic evidence. A previously reported causal effect of CRP on PTSD is potentially confounded by shared genetics. Together, results highlight the nuanced links between PTSD, autoimmune disorders, and associated inflammatory signatures, and suggest the importance of targeting related pathways to protect against disease and disability.

Dataset Information

Influence of genetically predicted autoimmune diseases on NAFLD.

Introduction

Methods

Result

Conclusion

Publications

Influence of genetically predicted autoimmune diseases on NAFLD.

Similar Datasets

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