Sun Yuxuan, Ding Ziyi, Guo Yawei, Yuan Jinqiu, Zhu Chengming, Pan Yihang, Sun Rui
Scientific Research Center, Sun Yat-sen University, The Seventh Affiliated Hospital, Shenzhen 518107, China.
The Herbert Wertheim School of Public Health and Longevity, University of California San Diego, La Jolla, CA 92093, USA.
J Clin Med. 2023 Feb 20;12(4):1681. 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.
我们评估了三种新冠肺炎表型与胰岛素样生长因子1、雌激素、睾酮、脱氢表雄酮（DHEA）、促甲状腺激素、促甲状腺激素释放激素、黄体生成素（LH）和卵泡刺激素之间的因果关联。我们使用双向双样本单变量和多变量孟德尔随机化（MR）分析来评估中枢神经系统调节激素与新冠肺炎表型之间关联的方向、特异性和因果关系。中枢神经系统调节激素的遗传工具是从欧洲人群最大的公开全基因组关联研究中选取的。新冠肺炎严重程度、住院情况和易感性的汇总数据来自新冠肺炎宿主遗传计划。在单变量MR中，DHEA与极重度呼吸综合征风险增加相关（比值比[OR]=4.21，95%置信区间[CI]：1.41 - 12.59），与多变量MR结果一致（OR = 3.72，95% CI：1.20 - 11.51），且与住院相关（OR = 2.31，95% CI：1.13 - 4.72）。在单变量MR中，LH与极重度呼吸综合征相关（OR = 0.83；95% CI：0.71 - 0.96）。在多变量MR中，雌激素与极重度呼吸综合征（OR = 0.09，95% CI：0.02 - 0.51）、住院（OR = 0.25，95% CI：0.08 - 0.78）和易感性（OR = 0.50，95% CI：0.28 - 0.89）呈负相关。我们发现了DHEA、LH和雌激素与新冠肺炎表型之间因果关系的有力证据。
