418-P: Allometric Body Shape Indices, T2D, and Kidney Function—A Two-Sample Mendelian Randomization Study

Abstract

In a two-sample Mendelian randomization (MR) analysis, using summary statistics from UK Biobank, CKDGen and DIAGRAM, we examined the association between BMI independent allometric body shape indices (a body shape index [ABSI], waist-hip index [WHI] and hip index [HI]) and kidney function (urinary albumin-to-creatinine ratio [UACR], estimated glomerular filtration rate and blood urea nitrogen). Furthermore, we investigated T2D as a potential mediator on the pathway to albuminuria. One standard deviation (SD) increase in genetically predicted ABSI and WHI levels was associated with higher UACR (β=0.039 [0.016, 0.063] log [UACR], p=0.001 for ABSI, and β=0.028 [0.012, 0.063] log [UACR], p=6×10-4 for WHI) in women, but not in men. Meanwhile, one 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<2×10-13) only, but decreased for genetically high HI in both sexes (p<2×10-4). No other associations were observed. 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. Disclosure A.D.Kjaergaard: None. J.Krakauer: None. N.Krakauer: None. A.Teumer: None. T.W.Winkler: None. C.Ellervik: None. Funding Novo Nordisk Foundation (22OC0076023)