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Mendelian randomization supports a causative effect of TSH on thyroid carcinoma.

ABSTRACT: Evidence from observational studies suggest a positive association between serum thyroid-stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause-effect relationship is poorly understood and these studies are susceptible to bias and confounding. This study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank participants, using a genetic technique, known as Mendelian randomization (MR). Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. Mendelian randomization provided evidence of a causal link between TSH and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that a 1 s.d. higher genetically instrumented TSH (approximately 0.8 mIU/L) resulted in 4.96-fold higher odds of benign nodular disease (95% CI 2.46-9.99) and 2.00-fold higher odds of thyroid cancer (95% CI 1.09-3.70). Our results thus support a causal role for TSH in both benign nodular thyroid disease and thyroid cancer.

SUBMITTER: Fussey JM

PROVIDER: S-EPMC7497356 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation. Methods Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program. Results According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34–0.96; false discovery rate [FDR] = 0.046), genus Family XIII AD3011 group (OR = 0.60; 95% CI, 0.39–0.91; FDR = 0.026), genus Prevotella 7 (OR = 0.73; 95% CI, 0.56–0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03–3.12; FDR = 0.061), genus Eggerthella group (OR = 1.34; 95% CI, 1.04–1.74; FDR = 0.043), genus Eubacterium ventriosum group (OR = 1.59; 95% CI, 1.01–2.51; FDR = 0.056), genus Holdemania (OR = 1.35; 95% CI, 1.00–1.82; FDR = 0.049), and genus Ruminococcus gauvreauii group (OR = 1.69; 95% CI, 1.10–2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs). Conclusion In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.

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Mendelian randomization supports a causative effect of TSH on thyroid carcinoma.

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