Sex‐specific causality of MRI ‐derived body compositions on glycaemic traits: Mendelian randomization and observational study
Authors' conclusion
Body composition has a sex-specific effect on type 2 diabetes, and higher GFATadj has an independent protective effect on type 2 diabetes in both sexes.
Study context
- Population
- Sex-specific GWAS summary statistics: MRI adipose deposits (20,038 women; 19,038 men) and ALMadj (244,730 women; 205,513 men), UK Biobank; T2D from DIAGRAM, fasting glucose and insulin from MAGIC
- Exposure
- Genetically predicted MRI-derived body composition (ASATadj, VATadj, GFATadj) and ALMadj vs T2D and glycaemic traits, by sex
- Outcome
- T2D and related glycaemic traits
Methodological detailssex-specific, univariable and multivariable Mendelian randomization (MR) (multivariable MR (MVMR)), validation with anthropometric MR and individual-level genetic association analyses
- Sex-specific
- Univariable and multivariable MR (MVMR)
- Validation with anthropometric MR and individual-level genetic association analyses
Main finding
As reported in the abstract
T2D, univariable MR, women
GFATadj, women: OR
0.59 (0.50, 0.69) (95% CI)
ALMadj, women: OR
0.84 (0.77, 0.91) (95% CI)
Observational data: associations, not effects.
Further findings
T2D, MVMR adjusted for ASATadj and VATadj
- GFATadj, women: OR (95% CI); P
- 0.57 (0.42, 0.77); P = 2.6 × 10-4
- GFATadj, men (nominally significant): OR (95% CI); P
- 0.58 (0.35, 0.96); P = 3.3 × 10-2
Validation analyses
- MR of anthropometric measures and genetic association analyses of glycaemic traits confirmed the results
Original publication
Sex‐specific causality of MRI ‐derived body compositions on glycaemic traits: Mendelian randomization and observational study. Diabetes Obes Metab. Published 3 November 2023. doi:10.
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