Use of bidirectional Mendelian randomization to unveil the association of Helicobacter pylori infection and autoimmune thyroid diseases.
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ABSTRACT:
SUBMITTER: Wang K
PROVIDER: S-EPMC11290481 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Use of bidirectional Mendelian randomization to unveil the association of <i>Helicobacter pylori</i> infection and autoimmune thyroid diseases.
Wang Kai K Wang Kai K Zhang Qinnan Q Zhang Panpan P Yang Qian Q Pan Fanfan F Zha Bingbing B
Science advances 20240731 31
Previous observational studies found associations between <i>Helicobacter pylori</i> infection and autoimmune thyroid diseases (AITDs), but the causal nature of this association is still uncertain. We investigated the causal effect of six crucial antibodies against <i>H. pylori</i> on AITDs using a bidirectional Mendelian randomization (MR). We found that anti-<i>H. pylori</i> outer membrane protein (OMP) significantly increased the risk of hyperthyroidism and Graves' disease (GD). In addition, ...[more]
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Project description:BackgroundObservational studies suggest the risk of primary ovarian insufficiency (POI) is increased in autoimmune disorders (AIDs), but it is unclear whether there is a causal relationship. Therefore, we aimed to investigate the bidirectional causality between 20 AIDs and POI using Mendelian randomization (MR) analysis.MethodsA bidirectional two-sample MR investigation was designed by using publicly accessible summary-level data from genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by several sensitivity analyses. Cochran Q test was used to evaluate SNP estimate heterogeneity. MR-Egger and MR-PRESSO methods were utilized to detect horizontal pleiotropy.ResultsThe MR analyses revealed that genetically determined coeliac disease (CeD) (OR = 1.124, 95% CI 1.033-1.224, P = 0.007), vitiligo (OR = 1.092, 95% CI 1.003-1.188; P = 0.042), systemic lupus erythematosus (SLE) (OR = 1.122, 95% CI 1.030-1.223, P = 0.008), and selective immunoglobulin A deficiency (SIgAD) (OR = 0.866, 95% CI: 0.776-0.967, P = 0.011) exhibited significant causal relationships with POI. We also found suggestive evidence of positive effect of Addison's disease (AD) towards POI (OR5e-6 = 1.076, 95% CI 1.002-1.154, P = 0.043).ConclusionThis comprehensive MR analysis indicated that SLE, CeD, vitiligo, and AD caused an increased risk of POI, SIgAD was associated with a decreased risk of POI. These insights carry profound clinical implications, particularly emphasizing the early intervention for women with AIDs/POI who wish to preserve their reproductive potential or plan for future pregnancies.
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Project description:Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained controversial. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to verify the causal association between AIDs and CRC. We employed three common MR approaches, including inverse variance weighted (IVW), weighted median, and MR-Egger methods, to assess the causal association between type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, juvenile idiopathic arthritis, celiac disease, and primary sclerosing cholangitis (PSC) and CRC. The reverse MR analysis was performed to assess the possibility of reverse causation. To evaluate the validity of the analysis, we also performed sensitivity analysis, such as the heterogeneity test, the horizontal pleiotropy test, and the leave-one-out sensitivity analysis, and validated the results in the validation cohort. Our results showed that genetically predicted T1D was nominally associated with a lower risk of CRC (IVW OR = 0.965, 95% CI = 0.939-0.992, P = 0.012). However, genetic susceptibility to psoriasis nominally increased the risk of CRC (IVW OR = 1.026, 95% CI = 1.002-1.050, P = 0.037). Genetically predicted PSC had a significant causal effect on the increasing risk of CRC (IVW OR = 1.038, 95% CI = 1.016-1.060, P = 5.85 × 10-4). Furthermore, the MR analysis between PSC and the CRC validation cohort indicated consistent results. We found no causal association between genetically predicted other five AIDs and CRC (P > 0.05). The results of reverse MR analysis showed that genetically predicted CRC had no causal effect on T1D, psoriasis, and PSC (P > 0.05). The sensitivity analysis demonstrated that the results of the MR analysis were reliable. Our findings help to understand the causal association between AIDs and CRC, which deserves further investigation.
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Project description:BackgroundAutoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive.MethodsA two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers.ResultsSeven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-β and low levels of stem cell growth factor-β were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1β, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, β-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels.ConclusionOur bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.
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