DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Circulating levels of micronutrients and risk of osteomyelitis: a Mendelian randomization study

Journal Article · · Frontiers in Nutrition

Background Few observational studies have investigated the effect of micronutrients on osteomyelitis, and these findings are limited by confounding and conflicting results. Therefore, we conducted Mendelian randomization (MR) analyses to evaluate the association between blood levels of eight micronutrients (copper, selenium, zinc, vitamin B12, vitamin C, and vitamin D, vitamin B6, vitamin E) and the risk of osteomyelitis. Methods We performed the two-sample and multivariable Mendelian randomization (MVMR) to investigate causation, where instrument variables for the predictor (micronutrients) were derived from the summary data of micronutrients from independent cohorts of European ancestry. The outcome instrumental variables were used from the summary data of European-ancestry individuals ( n  = 486,484). The threshold of statistical significance was set at p  < 0.00625. Results We found a significant causal association that elevated zinc heightens the risk of developing osteomyelitis in European ancestry individuals OR = 1.23 [95% confidence interval (CI) [1.07, 1.43]; p  = 4.26E-03]. Similarly, vitamin B6 showed a similar significant causal effect on osteomyelitis as a risk factor OR = 2.78 (95% CI [1.34, 5.76]; p  = 6.04E-03; in the secondary analysis). Post-hoc analysis suggested this result (vitamin B6). However, the multivariable Mendelian randomization (MVMR) provides evidence against the causal association between zinc and osteomyelitis OR = 0.98(95% CI [−0.11, 0.07]; p  = 7.20E-1). After searching in PhenoScanner, no SNP with confounding factors was found in the analysis of vitamin B6. There was no evidence of a reverse causal impact of osteomyelitis on zinc and vitamin B6. Conclusion This study supported a strong causal association between vitamin B6 and osteomyelitis while reporting a dubious causal association between zinc and osteomyelitis.

Sponsoring Organization:
USDOE Office of Electricity (OE), Advanced Grid Research & Development. Power Systems Engineering Research
OSTI ID:
2453933
Journal Information:
Frontiers in Nutrition, Journal Name: Frontiers in Nutrition Vol. 11; ISSN 2296-861X
Publisher:
Frontiers Media SACopyright Statement
Country of Publication:
Switzerland
Language:
English

References (41)

Selenium supplementation for critically ill adults journal July 2015
Vitamin C supplementation for prevention and treatment of pneumonia journal November 2021
A framework for the investigation of pleiotropy in two‐sample summary data Mendelian randomization journal January 2017
Medicare Reimbursement Attributable to Periprosthetic Joint Infection Following Primary Hip and Knee Arthroplasty journal June 2015
Iron availability and infection journal July 2009
Nutritional immunity beyond iron: a role for manganese and zinc journal April 2010
Baseline hypovitaminosis D is not associated with poor clinical outcomes in osteoarticular infections journal September 2014
The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases journal June 2016
Surgical site infection in orthopedic trauma: A case–control study evaluating risk factors and cost journal December 2015
Inflammation, vitamin B6 and related pathways journal February 2017
Osteomyelitis journal July 2004
How do bacterial cells ensure that metalloproteins get the correct metal? journal January 2009
The UK Biobank resource with deep phenotyping and genomic data journal October 2018
Mendelian randomization journal February 2022
Low plasma vitamin B-6 concentrations and modulation of coronary artery disease risk journal June 2004
Dietary vitamin B-6 restriction does not alter rates of homocysteine remethylation or synthesis in healthy young women and men1–4 journal March 2005
Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress journal March 2007
Multivariable Mendelian Randomization: The Use of Pleiotropic Genetic Variants to Estimate Causal Effects journal January 2015
Genome-wide association study identifies loci affecting blood copper, selenium and zinc journal May 2013
Mendelian randomization: genetic anchors for causal inference in epidemiological studies journal July 2014
‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?* journal February 2003
Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants journal September 2010
Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression journal April 2015
Factors Influencing Infection Rate in Open Fracture Wounds journal June 1989
Stress-Induced Hyperglycemia as a Risk Factor for Surgical-Site Infection in Nondiabetic Orthopedic Trauma Patients Admitted to the Intensive Care Unit journal January 2013
Orthopaedic infections: what have we learned? journal May 2023
Multivariable Mendelian Randomization and Mediation journal April 2020
Homocysteine‐lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease journal April 2007
Low vitamin B6 plasma levels, a risk factor for thrombosis, in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants journal January 2003
Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses journal February 2008
A review of instrumental variable estimators for Mendelian randomization journal August 2015
May osteoarticular infections be influenced by vitamin D status? An observational study on selected patients journal August 2015
Vitamin E and Respiratory Infection in the Elderly journal December 2004
A Multivariate Genome-Wide Association Analysis of 10 LDL Subfractions, and Their Response to Statin Treatment, in 1868 Caucasians journal April 2015
A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection journal January 2020
Zinc in Infection and Inflammation journal June 2017
Zinc as a Gatekeeper of Immune Function journal November 2017
Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies journal April 2016
Moderate Dietary Vitamin B-6 Restriction Raises Plasma Glycine and Cystathionine Concentrations While Minimally Affecting the Rates of Glycine Turnover and Glycine Cleavage in Healthy Men and Women journal March 2009
A Mathematical Model Gives Insights into the Effects of Vitamin B-6 Deficiency on 1-Carbon and Glutathione Metabolism journal April 2009
The Economic Significance of Orthopaedic Infections journal April 2015