Body composition and risk of gestational diabetes mellitus: A univariable and multivariable Mendelian randomization study.

Objective: In this study, we employed a Mendelian randomization (MR) approach to investigate the independent causal associations of six body composition traits with gestational diabetes mellitus (GDM).

Methods: Genome-wide significant levels (P < 10 × 5 ) of single nucleotide polymorphisms associated with body water mass, total protein, whole body fat-free mass, weight, whole body fat mass, and body fat percentage were used as instrumental variables. Data on GDM were obtained from the FinnGen Consortium, and both univariable and multivariable Mendelian randomization were performed. We utilized five different analytical methods including inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the robustness of the results.

Results: With univariable Mendelian randomization, the risk of GDM increased per 1-standard deviation (SD) increase in weight (OR  = 1.297, P = 3.06 × 10 ), whole body fat mass (OR  = 1.408, P = 1.32 × 10 ), and the risk of GDM increased per percent increase in body fat percentage (OR  = 1.661, P = 1.01 × 10 ). Total protein had a protective effect on the risk of GDM (OR  = 0.880, P = 0.048). However, there was no significant causal association between increases in body water mass and whole body fat-free mass per SD and the risk of GDM. Causal associations between weight, whole body fat mass, body fat percentage, and total protein with GDM were reduced to null in multivariable Mendelian randomization.

Conclusion: The present study furnishes genetic evidence to elucidate the causal relationship between body composition traits and GDM. Additionally, further studies are imperative to establish a causal connection between body composition traits and gestational diabetes mellitus.