A potentially causal relationship may exist between genetically predicted insomnia and the risk for sepsis. The association between insomnia and sepsis was more pronounced in women relative to men. These are the findings of a study published in JAMA Psychiatry.
Insomnia is a common sleep disorder that impacts immune function and inflammation. When the immune response is dysregulated, the risk for sepsis may increase. For the study, researchers sought to determine if genetically predicted insomnia is associated with the risk of developing sepsis.
The researchers used a 2-sample Mendelian randomization (MR) method — the Wald ratio was calculated for each single-nucleotide variant (SNV), defined as the SNV-outcome association divided by the SNV-exposure association.
Individuals of European ancestry were included in the study, with 555 genetic variants found from a genome-wide associated study (GWAS) to be strongly associated with insomnia and independent of one another.
The researchers extracted genetic associations for sepsis from a GWAS in the United Kingdom Biobank. For the main analysis, they used the inverse-variance weighted (IVW) method to calculate the combined association across the Wald ratios for all SNVs. The researchers also evaluated the proportion of the association between insomnia and sepsis that was mediated by body mass index (BMI), type 2 diabetes, smoking, and cardiovascular disease (CVD).
A total of 593,724 individuals with insomnia and 10,154 cases of sepsis were included in the study, with 3.9% of the variance of insomnia explained by the genetic variants used in the main analysis.
A genetically predicted doubling in insomnia prevalence was associated with an odds ratio (OR) for sepsis of 1.37 (95% CI, 1.19-1.57; P =7.6 x 10-6). One-third of the association between genetically predicted insomnia and risk for sepsis was mediated through BMI, type 2 diabetes, smoking, or CVD. When each cardiometabolic factor was analyzed separately, only BMI significantly mediated the association between genetically predicted insomnia and risk for sepsis. The link between insomnia and sepsis was more pronounced among women relative to men (women: OR, 1.44; 95% CI, 1.24-1.68; men: OR, 1.10; 95% CI, 0.86-1.40).
The findings from the study corroborate recent findings that linked insomnia and increased risk for altered immune response and bloodstream infection. Additionally, this study shows that the association between genetically predicted insomnia and risk for sepsis is mediated by cardiometabolic factors.
“However, most of the association between insomnia and risk of sepsis was not explained by these factors, indicating that insomnia may have a substantial direct influence on sepsis risk,” the researchers wrote.
A limitation of the study was that it only included individuals of European ancestry. The researchers noted that they “encourage future studies to evaluate whether our findings replicate in other ancestry groups.”
Thorkildsen MS, Gustad LT, Mohus RM, et al. Association of genetically predicted insomnia with risk of sepsis: a Mendelian randomization study. JAMA Psychiatry. Published online August 9, 2023. doi:10.1001/jamapsychiatry.2023.2717
This article originally appeared on Neurology Advisor