| Title: | Genetically predicted plasma cortisol and common chronic diseases: A Mendelian randomization study |
| Journal: | Clinical Endocrinology |
| Published: | 5 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37667866/ |
| DOI: | https://doi.org/10.1111/cen.14966 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cen.14966 |
Publication 9636
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Abstract
OBJECTIVE: Cushing's syndrome is characterized by hypercortisolaemia and is frequently accompanied by comorbidities such as type 2 diabetes, hypertension, osteoporosis, depression and schizophrenia. It is unclear whether moderate but lifelong hypercortisolaemia is causally associated with these diseases in the general population. We aimed to address this research gap using a Mendelian randomization approach.</p>
METHODS: We used three cortisol-associated genetic variants in the SERPINA6/SERPINA1 region as genetic instruments in a two-sample, inverse-variance-weighted Mendelian randomization analysis. We obtained summary-level statistics for cortisol and disease outcomes from publicly available genetic consortia, and meta-analysed them as appropriate. We conducted a multivariable Mendelian randomization analysis to assess potential mediating effects.</p>
RESULTS: A 1 standard deviation higher genetically predicted plasma cortisol was associated with greater odds of hypertension (odds ratio: 1.12; 95% confidence interval [CI]: 1.05-1.18) as well as higher systolic blood pressure (mean difference [MD]: 0.03 SD change; 95% CI: 0.01-0.05) and diastolic blood pressure (MD: 0.03 SD change; 95% CI: 0.01-0.04). There was no evidence of association with type 2 diabetes, osteoporosis, depression and schizophrenia. The association with hypertension was attenuated upon adjustment for waist circumference, suggesting potential mediation through central obesity.</p>
CONCLUSION: There is strong evidence for a causal association between plasma cortisol and greater risk for hypertension, potentially mediated by obesity.</p>
7 Authors
- Wei-Hsuan Lee
- Susanna C. Larsson
- Angela Wood
- Emanuele Di Angelantonio
- Adam S. Butterworth
- Stephen Burgess
- Elias Allara
1 Application
| Application ID | Title |
|---|---|
| 7439 | Comparissons of measures of adiposity including body-mass index, waist-circumference, waist-to-hip ratio, and percentage body fat mass |
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