JMIR Publications

ABSTRACT

Background:

Sepsis is a life-threatening condition characterized by organ dysfunction resulting from a dysregulated host response to infections. Approximately 48.9 million people worldwide are diagnosed with sepsis annually, leading to 11 million deaths and representing 19.7% of all global deaths. No specific effective treatments are available for sepsis, which has a poor prognosis.

Objective:

We aimed to systematically explore the relationship between genetically predicted modifiable risk factors and sepsis.

Methods:

Univariable two-sample Mendelian randomization (MR) analysis was performed to explore the relationship between 30 modifiable risk factors (12 lifestyle, 3 educational and psychological, and 15 metabolic factors) and sepsis. Heterogeneity was evaluated using Cochran's Q analysis. Sensitivity analyses were conducted using the MR-Egger regression intercept tests and leave-one-out analyses. Additionally, multivariable MR analyses were performed to adjust for genetic associations between the instruments and obesity.

Results:

Genetically predicted smoking (odds ratio, OR, 1.20; 95% confidence interval, CI, 1.06–1.36), higher number of cigarettes smoked daily (OR, 1.70; 95% CI, 1.29–2.23), higher overall health rating (OR, 2.19; 95% CI, 1.61–2.98), body mass index (OR, 1.50; 95% CI, 1.38–1.63), waist circumference (OR, 1.70; 95% CI, 1.53–1.89), whole body fat mass (OR, 1.50; 95% CI, 1.37–1.64), trunk fat mass (OR, 1.48; 95% CI, 1.36–1.62), arm fat mass (OR, 1.57; 95 %CI, 1.43–1.71), and leg fat mass (OR, 1.69; 95 % CI, 1.51–1.90) were associated with increased sepsis risk (all with P < 0.05). However, light physical activity (OR, 0.26; 95% CI, 0.08–0.83), higher education attainment (OR, 0.52; 95% CI, 0.40–0.67) and high-density lipoprotein-cholesterol (OR, 0.91; 95% CI, 0.84–0.98) exhibited a protective effect against sepsis (all with P < 0.05). In multivariate analysis of obesity traits, the waist circumference (OR = 2.16, 95% CI = 1.18–3.96, P = 0.01) was an independent risk factor of sepsis.

Conclusions:

Genetic predictors of smoking initiation, smoking frequency, and waist circumference were associated with an increased risk of sepsis. By contrast, higher education, light physical activity, and high-density lipoprotein-cholesterol levels were associated with a reduced risk of sepsis. Our results can serve as a guide for reducing the risk of sepsis.