Effects of testosterone and sex hormone binding globulin on lung function in males and females: a multivariable Mendelian Randomisation study
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| Název: | Effects of testosterone and sex hormone binding globulin on lung function in males and females: a multivariable Mendelian Randomisation study |
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| Autoři: | van der Plaat, Diana, Lenoir, Alexandra, Dharmage, Shyamali, Potts, James, Gómez Real, Francisco, Shaheen, Seif, Jarvis, Debbie, Minelli, Cosetta, Leynaert, Bénédicte |
| Přispěvatelé: | LEYNAERT, Bénédicte, National Heart and Lung Institute London (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital Lausanne (CHUV), University of Melbourne, University of Bergen (UiB), Haukeland University Hospital, Queen Mary University of London (QMUL), Barts & The London School of Medicine and Dentistry, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay |
| Zdroj: | Thorax. 79:564-572 |
| Informace o vydavateli: | BMJ, 2024. |
| Rok vydání: | 2024 |
| Témata: | Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Vital Capacity, 03 medical and health sciences, 0302 clinical medicine, Sex Hormone-Binding Globulin, Forced Expiratory Volume, GWAS, Humans, sex hormone-binding globulin, Testosterone, Obesity, Lung, Aged, 2. Zero hunger, lung function, Mendelian Randomization Analysis, Middle Aged, United Kingdom, Respiratory Function Tests, [SDV] Life Sciences [q-bio], multivariable Mendelian randomisation, Female, COPD epidemiology, Respiratory Measurement, Genome-Wide Association Study |
| Popis: | BackgroundObservational studies suggest that total testosterone (TT) and sex hormone-binding globulin (SHBG) may have beneficial effects on lung function, but these findings might be spurious due to confounding and reverse causation. We addressed these limitations by using multivariable Mendelian randomisation (MVMR) to investigate the independent causal effects of TT and SHBG on lung function.MethodsWe first identified genetic instruments by performing genome-wide association analyses of TT and SHBG in the large UK Biobank, separately in males and females. We then assessed the independent effects of TT and SHBG on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC using one-sample MVMR. We addressed pleiotropy, which could bias MVMR, using several methods that account for it. We performed subgroup MVMR analyses by obesity, physical activity and menopausal status, and assessed associations between TT and SHBG with lung function decline. Finally, we compared the MVMR results with those of observational analyses in the UK Biobank.FindingsIn the MVMR analyses, there was evidence of pleiotropy, but results were consistent when accounting for it. We found a strong beneficial effect of TT on FVC and FEV1in both males and females, but a moderate detrimental effect of SHBG on FEV1and FEV1/FVC in males only. Subgroup analyses suggested stronger effects of TT among obese and older males. The observational analyses, in line with previous studies, agreed with MRMV for TT, but not for SHBG.InterpretationThese findings suggest that testosterone improves lung function in males and females, while SHBG has an opposite independent effect in males. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1468-3296 0040-6376 |
| DOI: | 10.1136/thorax-2023-220374 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38418196 https://inserm.hal.science/inserm-04495530v1 https://doi.org/10.1136/thorax-2023-220374 https://inserm.hal.science/inserm-04495530v1/document |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....a06248b075513d443a7d8a50db5f05e0 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | BackgroundObservational studies suggest that total testosterone (TT) and sex hormone-binding globulin (SHBG) may have beneficial effects on lung function, but these findings might be spurious due to confounding and reverse causation. We addressed these limitations by using multivariable Mendelian randomisation (MVMR) to investigate the independent causal effects of TT and SHBG on lung function.MethodsWe first identified genetic instruments by performing genome-wide association analyses of TT and SHBG in the large UK Biobank, separately in males and females. We then assessed the independent effects of TT and SHBG on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC using one-sample MVMR. We addressed pleiotropy, which could bias MVMR, using several methods that account for it. We performed subgroup MVMR analyses by obesity, physical activity and menopausal status, and assessed associations between TT and SHBG with lung function decline. Finally, we compared the MVMR results with those of observational analyses in the UK Biobank.FindingsIn the MVMR analyses, there was evidence of pleiotropy, but results were consistent when accounting for it. We found a strong beneficial effect of TT on FVC and FEV1in both males and females, but a moderate detrimental effect of SHBG on FEV1and FEV1/FVC in males only. Subgroup analyses suggested stronger effects of TT among obese and older males. The observational analyses, in line with previous studies, agreed with MRMV for TT, but not for SHBG.InterpretationThese findings suggest that testosterone improves lung function in males and females, while SHBG has an opposite independent effect in males. |
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| ISSN: | 14683296 00406376 |
| DOI: | 10.1136/thorax-2023-220374 |