GENETIC PREDICTION OF CAUSAL RELATIONSHIPS BETWEEN OSTEOPOROSIS AND SEPSIS: EVIDENCE FROM MENDELIAN RANDOMIZATION WITH TWO-SAMPLE DESIGNS.

Abstract: Background: Recent observational studies have suggested that osteoporosis may be a risk factor for sepsis. To mitigate confounding factors and establish the causal relationship between sepsis and osteoporosis, we conducted a two-sample Mendelian randomization analysis using publicly available summary statistics. Methods: Utilizing summary data from FinnGen Biobank, we employed a two-sample Mendelian randomization (MR) analysis to predict the causal relationship between osteoporosis and sepsis. The MR analysis primarily utilized the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode analyses, with Bayesian weighted MR (BWMR) analysis employed for result validation. Sensitivity analyses included MR-PRESSO, "leave-one-out" analysis, MR-Egger regression, and Cochran Q test. Results: In the European population, an increase of one standard deviation in osteoporosis was associated with an 11% increased risk of sepsis, with an odds ratio (OR) of 1.11 (95% CI, 1.06-1.16; P = 3.75E-06). BWMR yielded an OR of 1.11 (95% CI, 1.06-1.67; P = 1.21E-05), suggesting osteoporosis as a risk factor for sepsis. Conversely, an increase of one standard deviation in sepsis was associated with a 26% increased risk of osteoporosis, with an OR of 1.26 (95% CI, 1.11-1.16; P = 0.45E-03). BWMR yielded an OR of 1.26 (95% CI, 1.09-1.45; P = 1.45E-03), supporting sepsis as a risk factor for osteoporosis. Conclusion: There is an association between osteoporosis and sepsis, with osteoporosis serving as a risk factor for the development of sepsis, while sepsis may also promote the progression of osteoporosis.