TY - JOUR
T1 - Genetically predicted high IGF-1 levels showed protective effects on COVID-19 susceptibility and hospitalization
T2 - a Mendelian randomisation study with data from 60 studies across 25 countries
AU - Li, Xinxuan
AU - Zhou, Yajing
AU - Yuan, Shuai
AU - Zhou, Xuan
AU - Wang, Lijuan
AU - Sun, Jing
AU - Yu, Lili
AU - Zhu, Jinghan
AU - Zhang, Han
AU - Yang, Nan
AU - Dai, Shuhui
AU - Song, Peige
AU - Larsson, Susanna C
AU - Theodoratou, Evropi
AU - Zhu, Yiming
AU - Li, Xue
N1 - Funding Information:
Natural Science Foundation of Zhejiang Province
Funding Information:
The authors are thankful for all the participants that contributed to the UK Biobank study. Funding Statement: The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication Funding information: This paper was supported by the following grants: Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) to Xue Li. CRUK Career Development Fellowship(C31250/A22804) to Evropi Theo-doratou, the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden) to Susanna C Larsson.
Publisher Copyright:
© Li et al.
PY - 2022/10/17
Y1 - 2022/10/17
N2 - Background: Epidemiological studies observed gender differences in COVID-19 outcomes, however, whether sex hormone plays a causal in COVID-19 risk remains unclear. This study aimed to examine associations of sex hormone, sex hormones-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and COVID-19 risk.Methods: Two-sample Mendelian randomization (TSMR) study was performed to explore the causal associations between testosterone, estrogen, SHBG, IGF-1, and the risk of COVID-19 (susceptibility, hospitalization, and severity) using genome-wide association study (GWAS) summary level data from the COVID-19 Host Genetics Initiative (N=1,348,701). Random-effects inverse variance weighted (IVW) MR approach was used as the primary MR method and the weighted median, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test were conducted as sensitivity analyses.Results: Higher genetically predicted IGF-1 levels have nominally significant association with reduced risk of COVID-19 susceptibility and hospitalization. For one standard deviation increase in genetically predicted IGF-1 levels, the odds ratio was 0.77 (95% confidence interval [CI], 0.61-0.97, p=0.027) for COVID-19 susceptibility, 0.62 (95% CI: 0.25-0.51, p=0.018) for COVID-19 hospitalization, and 0.85 (95% CI: 0.52-1.38, p=0.513) for COVID-19 severity. There was no evidence that testosterone, estrogen, and SHBG are associated with the risk of COVID-19 susceptibility, hospitalization, and severity in either overall or sex-stratified TSMR analysis.Conclusions: Our study indicated that genetically predicted high IGF-1 levels were associated with decrease the risk of COVID-19 susceptibility and hospitalization, but these associations did not survive the Bonferroni correction of multiple testing. Further studies are needed to validate the findings and explore whether IGF-1 could be a potential intervention target to reduce COVID-19 risk.Funding: We acknowledge support from NSFC (LR22H260001), CRUK (C31250/A22804), SHLF (Hjärt-Lungfonden, 20210351), VR (Vetenskapsrådet, 2019-00977), and SCI (Cancerfonden).
AB - Background: Epidemiological studies observed gender differences in COVID-19 outcomes, however, whether sex hormone plays a causal in COVID-19 risk remains unclear. This study aimed to examine associations of sex hormone, sex hormones-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and COVID-19 risk.Methods: Two-sample Mendelian randomization (TSMR) study was performed to explore the causal associations between testosterone, estrogen, SHBG, IGF-1, and the risk of COVID-19 (susceptibility, hospitalization, and severity) using genome-wide association study (GWAS) summary level data from the COVID-19 Host Genetics Initiative (N=1,348,701). Random-effects inverse variance weighted (IVW) MR approach was used as the primary MR method and the weighted median, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test were conducted as sensitivity analyses.Results: Higher genetically predicted IGF-1 levels have nominally significant association with reduced risk of COVID-19 susceptibility and hospitalization. For one standard deviation increase in genetically predicted IGF-1 levels, the odds ratio was 0.77 (95% confidence interval [CI], 0.61-0.97, p=0.027) for COVID-19 susceptibility, 0.62 (95% CI: 0.25-0.51, p=0.018) for COVID-19 hospitalization, and 0.85 (95% CI: 0.52-1.38, p=0.513) for COVID-19 severity. There was no evidence that testosterone, estrogen, and SHBG are associated with the risk of COVID-19 susceptibility, hospitalization, and severity in either overall or sex-stratified TSMR analysis.Conclusions: Our study indicated that genetically predicted high IGF-1 levels were associated with decrease the risk of COVID-19 susceptibility and hospitalization, but these associations did not survive the Bonferroni correction of multiple testing. Further studies are needed to validate the findings and explore whether IGF-1 could be a potential intervention target to reduce COVID-19 risk.Funding: We acknowledge support from NSFC (LR22H260001), CRUK (C31250/A22804), SHLF (Hjärt-Lungfonden, 20210351), VR (Vetenskapsrådet, 2019-00977), and SCI (Cancerfonden).
KW - COVID-19/epidemiology
KW - Estrogens
KW - Genome-Wide Association Study
KW - Gonadal Steroid Hormones
KW - Hospitalization
KW - Humans
KW - Insulin-Like Growth Factor I/genetics
KW - Polymorphism, Single Nucleotide
KW - Testosterone
U2 - 10.7554/eLife.79720
DO - 10.7554/eLife.79720
M3 - Article
C2 - 36250974
SN - 2050-084X
VL - 11
JO - eLIFE
JF - eLIFE
M1 - e79720
ER -