The causal relationship between body composition indexes and primary membranous nephropathy: A bidirectional...

The present study aimed to explore the causal association between body composition indexes and primary membranous nephropathy (PMN) from a genetic perspective.

A bidirectional two-sample Mendelian randomization (MR) analysis was conducted in the present study. Genetic data were obtained from published genome-wide association studies on PMN (n = 7,979) and body composition indexes, including weight (n = 797,859), body mass index (n = 461,460), body fat percentage (n = 454,633), waist circumference (n = 568,740), hip circumference (n = 336,601), and basal metabolic rate (n = 454,874) in European populations. The inverse variance weighted (IVW) random-effects MR method was performed as the main analysis, with MR-Egger and weighted median methods used as supplemental methods. Several sensitivity analyses were used to examine the reliability of the findings.

The MR analysis results showed that weight (MRC-IEU: odds ratio (OR) = 1.578, 95% confidence interval (CI) = 1.047 - 2.379, and IVW p = 0.029; Neale Lab: OR = 1.745, 95% CI = 1.204 - 2.529, and IVW p = 0.003), body fat percentage (OR = 2.487, 95% CI = 1.349 - 4.583, and IVW p = 0.003), waist circumference (Neale Lab: OR = 1.700, 95% CI = 1.042 - 2.774, and IVW p = 0.034; GIANT: OR = 1.915, 95% CI = 1.030 - 3.559, and IVW p = 0.040), and hip circumference (OR = 1.410, 95% CI = 1.021 - 1.948, and IVW p = 0.037) were causally related to an increased risk of PMN. Sensitivity analysis verified and indicated the robustness of these results. Reverse MR analysis indicated no causal relationship between PMN and the body composition indexes.

The present study demonstrated causal relationships between body composition indexes and PMN, suggesting the potential value of these factors in helping to understand PMN and develop intervention strategies.