Causal association between thyroid dysfunction and sepsis: a two-sample mendelian randomization study.

Area of Science:

• Endocrinology
• Infectious Disease Epidemiology
• Genetic Epidemiology

Background:

• The relationship between thyroid dysfunction (hyperthyroidism, hypothyroidism) and sepsis remains debated.
• Previous studies have yielded controversial findings regarding this association.

Purpose of the Study:

• To investigate the causal association between hyperthyroidism or hypothyroidism and susceptibility to four distinct sepsis subtypes using Mendelian randomization.
• To explore potential reverse causality between hypothyroidism and specific sepsis subtypes.

Main Methods:

• Two-sample Mendelian randomization (MR) analyses were performed using genome-wide association studies (GWAS) data.
• Instrumental variables were derived from large-scale genetic databases.
• Sensitivity analyses and inverse MR were conducted to assess robustness and rule out reverse causality.

Main Results:

• Hypothyroidism showed a causal relationship with asthma-associated pneumonia or sepsis (OR=1.097) and other sepsis (OR=1.070).
• No causal link was found between hypothyroidism and streptococcal or puerperal sepsis.
• No evidence of a causal association between hyperthyroidism and any of the studied sepsis subtypes was observed.

Conclusions:

• Hypothyroidism is causally associated with asthma-associated pneumonia or sepsis and other sepsis.
• There is no evidence of a causal relationship between hyperthyroidism and the studied sepsis subtypes.
• The findings contribute to understanding the complex interplay between thyroid function and sepsis risk.