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

• Published in: Journal of clinical medicine Vol. 12; no. 4; p. 1681
• Main Authors: Sun, Yuxuan, Ding, Ziyi, Guo, Yawei, Yuan, Jinqiu, Zhu, Chengming, Pan, Yihang, Sun, Rui
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Analysis; Asymptomatic; Central nervous system; CNS-regulated hormones; Confounding (Statistics); Coronaviruses; COVID-19; COVID-19 vaccines; Cytokines; Disease; Dosage and administration; Estrogens; Genomes; Health aspects; Hormone therapy; Hormones; Hospitalization; Infections; Mendelian randomization; Mortality; Observational studies; Phenotype; Physiological aspects; Severe acute respiratory syndrome coronavirus 2; Testing; Testosterone; Thyroid gland; China; COVID-19; CNS-regulated hormones; Mendelian randomization
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm12041681

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.