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Tytuł:
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Causal effect of sex hormone-binding globulin and testosterone on coronary heart disease: A multivariable and network Mendelian randomization analysis.
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Autorzy:
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Li Y; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Si S; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Hou L; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Yuan T; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Chen X; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Liu C; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Li W; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Li H; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China; Institute for Medical Dataology, Shandong University, Jinan 250002, PR China.
Liu Y; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China; Institute for Medical Dataology, Shandong University, Jinan 250002, PR China. Electronic address: .
Xue F; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China; Institute for Medical Dataology, Shandong University, Jinan 250002, PR China. Electronic address: .
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Źródło:
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International journal of cardiology [Int J Cardiol] 2021 Sep 15; Vol. 339, pp. 179-184. Date of Electronic Publication: 2021 Jun 25.
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Typ publikacji:
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Journal Article; Meta-Analysis
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Język:
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English
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Imprint Name(s):
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Publication: Amsterdam : Elsevier
Original Publication: Amsterdam : Elsevier/North-Holland Biomedical Press, c1981-
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MeSH Terms:
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Coronary Disease*/epidemiology
Coronary Disease*/genetics
Sex Hormone-Binding Globulin*
Humans ; Male ; Mendelian Randomization Analysis ; Risk Factors ; Testosterone
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Contributed Indexing:
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Keywords: Causal effect; Coronary heart disease; Mendelian randomization; SHBG; Testosterone
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Substance Nomenclature:
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0 (Sex Hormone-Binding Globulin)
3XMK78S47O (Testosterone)
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Entry Date(s):
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Date Created: 20210628 Date Completed: 20211020 Latest Revision: 20211020
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Update Code:
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20240105
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DOI:
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10.1016/j.ijcard.2021.06.037
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PMID:
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34181993
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Background: Although observational studies have shown an association between sex hormone-binding globulin (SHBG), testosterone (T) and cardiovascular diseases (CVD), controversy remains. In this study, we aim to explore the causal effects of SHBG and T on Coronary heart disease (CHD).
Methods: We used univariable, network and multivariable mendelian randomization (MR) analysis to investigate the causal effect of SHBG and T on CHD. We performed inverse variance weighted (IVW) MR as the primary analysis, with the robustness of this approach further tested by other methods in sensitivity analysis. The SHBG and T were collected from the UK Biobank data, about 180,000 men aged 40 to 69 years. CHD was collected from CARDIoGRAMplusC4D 1000 Genomes-based GWAS, which was a meta-analysis including 48 studies and involving 60,801 CHD cases and 123,504 controls.
Results: Using univariable MR-IVW, the results suggested that a one standard deviation (SD) increase in SHBG, the risk of CHD decreased by approximately 14% (OR (95% CI): 0.86(0.76,0.97)), and that a SD increase in total testosterone (TT), the risk also decreased, approximately 8% (OR (95% CI): 0.92(0.85,0.99)). Multivariable MR showed that both SHBG and TT had no direct causal effect with CHD (a SD increase in SHBG: OR (95% CI):0.75(0.57,1.00), P = 0.053; a SD increase in TT: OR (95% CI): 1.05(0.90,1.22), P = 0.53). In the network MR analysis, the results suggested that TT might act as mediator in the causal pathway from SHBG to CHD and account for 93% of the total effect of SHBG on CHD, and that SHBG might be a mediator in the causal pathway from TT to CHD and account for 67% of the total effect of TT on CHD.
Conclusions: Genetically predicted SHBG and TT were negatively correlated with CHD in both univariable and network MR, which may provide a causal explanation behind the observed conclusion. In addition, TT and SHBG had a bidirectional causal effect. Further work is required to disentangle the downstream effects of SHBG/TT on CHD and the molecular pathways involved, as the simultaneous regulation of SHBG and TT may make it a viable strategy for the prevention or treatment of CHD.
(Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
