Causal Inference of Central Nervous System-Regulated Hormones in COVID-19: A Bidirectional Two-Sample Mendelian Randomization Study

Abstract

We assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1, estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone, thyrotropin-releasing hormone, luteinizing hormone (LH), and follicle-stimulating hormone. We used bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analyses to evaluate the direction, specificity, and causality of the association between CNS-regulated hormones and COVID-19 phenotypes. Genetic instruments for CNS-regulated hormones were selected from the largest publicly available genome-wide association studies of the European population. Summary-level data on COVID-19 severity, hospitalization, and susceptibility were obtained from the COVID-19 host genetic initiative. DHEA was associated with increased risks of very severe respiratory syndrome (odds ratio [OR] = 4.21, 95% confidence interval [CI]: 1.41–12.59), consistent with multivariate MR results (OR = 3.72, 95% CI: 1.20–11.51), and hospitalization (OR = 2.31, 95% CI: 1.13–4.72) in univariate MR. LH was associated with very severe respiratory syndrome (OR = 0.83; 95% CI: 0.71–0.96) in univariate MR. Estrogen was negatively associated with very severe respiratory syndrome (OR = 0.09, 95% CI: 0.02–0.51), hospitalization (OR = 0.25, 95% CI: 0.08–0.78), and susceptibility (OR = 0.50, 95% CI: 0.28–0.89) in multivariate MR. We found strong evidence for the causal relationship of DHEA, LH, and estrogen with COVID-19 phenotypes.

The Influence of Autoimmune Thyroid Diseases on Viral Pneumonia Development, Including COVID-19: A Two-Sample Mendelian Randomization Study

“…These findings are in alignment with previous cross-sectional studies [ 12 , 62 , 63 , 64 ], indicating that alterations in isolated thyroid function indicators alone may not be sufficient to reliably predict the development of viral pneumonia or COVID-19. Prior to this study, four MR investigations examined the relationship between thyroid hormones and COVID-19, utilizing data from the fifth round of the Human Genetics of Infectious Diseases (HGI) releases [ 31 , 65 , 66 , 67 ]. In 2023, Sun et al employed an MR model to assess the causal link between TSH levels and three COVID-19 phenotypes and concluded that there was no association between TSH and COVID-19 [ 65 ], a conclusion consistent with our research.…”

“…Prior to this study, four MR investigations examined the relationship between thyroid hormones and COVID-19, utilizing data from the fifth round of the Human Genetics of Infectious Diseases (HGI) releases [ 31 , 65 , 66 , 67 ]. In 2023, Sun et al employed an MR model to assess the causal link between TSH levels and three COVID-19 phenotypes and concluded that there was no association between TSH and COVID-19 [ 65 ], a conclusion consistent with our research. Compared to previous studies, our analysis utilized data from the seventh round, which had a larger sample size than the fifth round.…”

Causal relationship between psoriasis vulgaris and dementia: Insights from Mendelian randomization analysis

“…15 MVMR analysis can be carried out to identify and elucidate potential confounding factors. 16 This study used the UVMR method based on GWAS data to analyse whether there is a causal effect between psoriasis vulgaris and dementia. Moreover, MVMR analyses were conducted to investigate the potential confounding effect of platelet-related indices, Vitamin D level and 25 hydroxyvitamin D level on the causal association between psoriasis vulgaris and VaD.…”

“…MVMR can estimate the causal effects of multiple exposures which may be closely interrelated 15 . MVMR analysis can be carried out to identify and elucidate potential confounding factors 16 …”