1. Allometric body shape indices, type 2 diabetes and kidney function: A two‐sample Mendelian randomization study.
- Author
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Kjaergaard, Alisa D., Krakauer, Jesse, Krakauer, Nir, Teumer, Alexander, Winkler, Thomas W., and Ellervik, Christina
- Subjects
TYPE 2 diabetes ,KIDNEY physiology ,RANDOMIZATION (Statistics) ,BLOOD urea nitrogen ,GLOMERULAR filtration rate ,KIDNEYS ,BODY mass index - Abstract
Aim: To examine the association between body mass index (BMI)‐independent allometric body shape indices and kidney function. Materials and methods: We performed a two‐sample Mendelian randomization (MR) analysis, using summary statistics from UK Biobank, CKDGen and DIAGRAM. BMI‐independent allometric body shape indices were: A Body Shape Index (ABSI), Waist‐Hip Index (WHI) and Hip Index (HI). Kidney function outcomes were: urinary albumin‐to‐creatinine ratio (UACR), estimated glomerular filtration rate and blood urea nitrogen. Furthermore, we investigated type 2 diabetes (T2D) as a potential mediator on the pathway to albuminuria. The main analysis was inverse variance‐weighted random‐effects MR in participants of European ancestry. We also performed several sensitivity MR analyses. Results: A 1‐standard deviation (SD) increase in genetically predicted ABSI and WHI levels was associated with higher UACR (β = 0.039 [95% confidence interval: 0.016, 0.063] log [UACR], P = 0.001 for ABSI, and β = 0.028 [0.012, 0.044] log [UACR], P = 6 x 10−4 for WHI) in women, but not in men. Meanwhile, a 1‐SD increase in genetically predicted HI was associated with lower UACR in women (β = −0.021 [−0.041, 0.000] log [UACR], P = 0.05) and in men (β = −0.026 [−0.058, 0.005] log [UACR], P = 0.10). Corresponding estimates in individuals with diabetes were substantially augmented. Risk of T2D increased for genetically high ABSI and WHI in women (P < 6 x 10−19) only, but decreased for genetically high HI in both sexes (P < 9 x 10−3). No other associations were observed. Conclusions: Genetically high HI was associated with decreased risk of albuminuria, mediated through decreased T2D risk in both sexes. Opposite associations applied to genetically high ABSI and WHI in women only. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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