[Causal relationship between thyroid dysfunction and sepsis: a bidirectional two-sample Mendelian randomization].

Area of Science:

• Genetics and Medicine
• Endocrinology
• Infectious Diseases

Background:

• Thyroid dysfunction, encompassing hypothyroidism and hyperthyroidism, affects numerous individuals globally.
• Sepsis is a life-threatening condition requiring urgent medical attention.
• The potential causal links between thyroid disorders and sepsis risk remain incompletely understood.

Purpose of the Study:

• To investigate the potential causal relationship between thyroid dysfunction (hypothyroidism and hyperthyroidism) and sepsis.
• To utilize a bidirectional two-sample Mendelian randomization (MR) approach for robust genetic association analysis.

Main Methods:

• Employed genome-wide association study (GWAS) datasets to identify single nucleotide polymorphisms (SNPs) as instrumental variables (IVs).
• Applied the inverse-variance weighted (IVW) method for primary MR analysis, with MR Egger regression and MR-PRESSO for pleiotropy and outlier detection.
• Conducted sensitivity analyses, including "leave one out" and reverse MR, to ensure result validity and explore bidirectional causality.

Main Results:

• 101 SNPs associated with hypothyroidism and 10 SNPs with hyperthyroidism were included in the MR analysis.
• Hypothyroidism was significantly associated with an increased risk of sepsis (OR = 2.293, P = 0.012).
• No significant causal relationship was found between hyperthyroidism and sepsis risk (OR = 1.049, P = 0.560), with sensitivity analyses confirming result stability.

Conclusions:

• Hypothyroidism is a significant risk factor for developing sepsis.
• There is no evidence of a causal link between hyperthyroidism and sepsis onset.
• Findings support targeted monitoring for sepsis risk in patients with hypothyroidism.