# Exploring the relationship between life course adiposity and sepsis: insights from a two-sample Mendelian randomization analysis

## TL;DR

This study finds that higher body fat in childhood and adulthood increases the risk of sepsis, using genetic data to suggest a causal link.

## Contribution

The study provides novel causal evidence linking life course adiposity to sepsis using Mendelian randomization.

## Key findings

- Genetic predisposition to higher childhood BMI increases sepsis risk (OR = 1.29, P = 0.003).
- Adult BMI and visceral adiposity show strong causal associations with sepsis (OR = 1.38 and 1.53, respectively).
- Sensitivity analyses confirm the robustness of the MR results without significant bias.

## Abstract

The relationship between adiposity and sepsis has received increasing attention. This study aims to explore the causal relationship between life course adiposity and the sepsis incidence.

Mendelian randomization (MR) method was employed in this study. Instrumental variants were obtained from genome-wide association studies for life course adiposity, including birth weight, childhood body mass index (BMI), childhood obesity, adult BMI, waist circumference, visceral adiposity, and body fat percentage. A meta-analysis of genome-wide association studies for sepsis including 10,154 cases and 454,764 controls was used in this study. MR analyses were performed using inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. Instrumental variables were identified as significant single nucleotide polymorphisms at the genome-wide significance level (P < 5×10-8). The sensitivity analysis was conducted to assess the reliability of the MR estimates.

Analysis using the MR analysis of inverse variance weighted method revealed that genetic predisposition to increased childhood BMI (OR = 1.29, P = 0.003), childhood obesity (OR = 1.07, P = 0.034), adult BMI (OR = 1.38, P < 0.001), adult waist circumference (OR = 1.01, P = 0.028), and adult visceral adiposity (OR = 1.53, P < 0.001) predicted a higher risk of sepsis. Sensitivity analysis did not identify any bias in the MR results.

The results demonstrated that adiposity in childhood and adults had causal effects on sepsis incidence. However, more well-designed studies are still needed to validate their association.