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Genetic Predisposition Between COVID-19 and Four Mental Illnesses: A Bidirectional, Two-Sample Mendelian Randomization Study

ABSTRACT: Background: The outbreak of 2019 coronavirus disease (COVID-19) has become a global pandemic. Although it has long been suspected that COVID-19 could contribute to the development of mental illness, and individuals with a pre-existing mental illness may have a higher risk of and poorer outcomes from COVID-19 infection, no evidence has established a causal association between them thus far. Methods: To investigate associations in support of a causal association between the severity of COVID-19 and mental illnesses, we leveraged large-scale genetic summary data from genome-wide association study (GWAS) summary datasets, including attention-deficit/hyperactivity disorder (ADHD) (n = 55,374), schizophrenia (n = 77,096), bipolar disorder (n = 51,710), and depression (n = 173,005), based on a previous observational study. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and MR-Egger approaches and multiple sensitivity analyses assessing horizontal pleiotropy and removing outliers in two different COVID-19 databases. Results: The Mendelian randomization (MR) analysis indicated that ADHD [odds ratio (OR) = 1.297; 95% confidence interval (CI), 1.029–1.634; p = 0.028] increased the risk of hospitalization due to COVID-19. A similar association was obtained in MR sensitivity analyses of the weighted median. In addition, genetically predicted COVID-19 was significantly associated with schizophrenia (OR = 1.043; 95% CI, 1.005–1.082; p = 0.027). Conclusions: Although many studies have reported a causal relationship between COVID-19 and mental illness, our study shows that this increased risk is modest. However, considering the characteristics of ADHD that might further increase the individuals' vulnerability to being infected by COVID-19, the ongoing massive worldwide exposure to COVID-19, and the high burden of schizophrenia, we believe that it is necessary to offer preventative measures to these populations and to provide more evidence in understanding the neurological impact of COVID-19.

SUBMITTER: Liu N

PROVIDER: S-EPMC8564104 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundObservational studies have demonstrated an association between primary sclerosing cholangitis (PSC) and thyroid dysfunction (TD). However, the causal relationship between PSC and TD remains uncertain. The purpose of this study is to investigate the causal associations and specific direction between these two conditions. Gaining insight into the potential causal relationship between PSC and TD is valuable for elucidating the pathogenesis of PSC and for devising innovative approaches for the prevention and treatment of PSC and its associated complications.MethodsWe conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between PSC and TD, such as autoimmune thyroid disease (AITD), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), among others. PSC was the exposure variable, while TD was the outcome variable. To identify suitable instrumental variables (IVs), we utilized genome-wide association study (GWAS) datasets to select potential candidate single-nucleotide polymorphisms (SNPs). The primary statistical approach employed was the inverse-variance weighted (IVW) method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy.ResultsWe found that the causal associations between genetically predicted PSC and Graves' disease (GD), hyperthyroidism (IVW OR=1.230, 95%CI: 1.089-1.389, P=0.001; IVW OR=1.001, 95%CI: 1.000-1.002, P=0.000) were statistically significant. The reverse MR analysis indicated that genetic susceptibility to hyperthyroidism (P=0.000) and hypothyroidism (p=0.028) might be the risk of PSC. There was no statistically significant causal association observed between PSC and other TD (IVW P>0.05), with the exception of GD, hyperthyroidism, and hypothyroidism as determined through bidirectional two-sample analysis. To ensure the reliability of our findings, additional sensitivity analyses were conducted, including the leave-one-out (LOO) test, heterogeneity test, and pleiotropic test.ConclusionIn this study, we conducted an investigation into the causal association between PSC and TD. Our findings indicate that PSC significantly elevates the susceptibility to GD and hyperthyroidism from a statistical perspective. These results shed light on the etiology of PSC and have implications for the management of patients with PSC.

Project description:BackgroundAlthough previous studies have suggested a close association between gut microbiota (GM) and intervertebral disc degeneration (IVDD), the causal relationship between them remains unclear. Hence, we thoroughly investigate their causal relationship by means of a two-sample Mendelian randomization (MR) study, aiming to determine the impact of gut microbiota on the risk of developing intervertebral disc degeneration.MethodsSummary data from genome-wide association studies of GM (the MiBioGen) and IVDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. A reverse MR analysis was conducted to assess potential reverse causation.ResultsWe identified nine gut microbial taxa that were causally associated with IVDD (P < 0.05). Following the Benjamini-Hochberg corrected test, the association between the phylum Bacteroidetes and a higher risk of IVDD remained significant (IVW FDR-corrected P = 0.0365). The results of the Cochrane Q test did not indicate heterogeneity (P > 0.05). Additionally, both the MR-Egger intercept test and the MR-PRESSO global test revealed that our results were not influenced by horizontal pleiotropy (P > 0.05). Furthermore, the leave-one-out analysis substantiated the reliability of the causal relationship. In the reverse analysis, no evidence was found to suggest that IVDD has an impact on the gut microbiota.ConclusionOur results validate the potential causal impact of particular GM taxa on IVDD, thus providing fresh insights into the gut microbiota-mediated mechanism of IVDD and laying the groundwork for further research into targeted preventive measures.

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Genetic Predisposition Between COVID-19 and Four Mental Illnesses: A Bidirectional, Two-Sample Mendelian Randomization Study

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