Causal link between folic acid and recurrent aphthous ulcers: A two-sample Mendelian randomization study.

Area of Science:

• Genetics
• Nutritional Science
• Oral Medicine

Background:

• Observational studies suggest links between micronutrient status and recurrent aphthous ulcers (RAU).
• The causal relationship between micronutrients and RAU remains unclear.
• Mendelian randomization (MR) offers a method to explore potential causal associations using genetic variants.

Purpose of the Study:

• To genetically evaluate the association between circulating micronutrients and RAU risk.
• To employ a two-sample MR approach using genome-wide association study (GWAS) data.
• To investigate 15 different micronutrients for their potential impact on RAU.

Main Methods:

• Two-sample Mendelian randomization analysis utilizing GWAS summary statistics.
• Genetic instruments for 15 micronutrients sourced from the IEU OpenGWAS database.
• RAU outcome data from the FinnGen consortium (5394 cases).
• Primary analysis using the Inverse Variance Weighted (IVW) method, with Weighted Median and MR-Egger for sensitivity.
• Sensitivity analyses to assess heterogeneity and horizontal pleiotropy.

Main Results:

• A nominally significant association was found between genetically predicted folic acid levels and increased RAU risk (OR=2.05, P=0.009) via the IVW method.
• Other MR methods indicated a consistent direction of effect but with wide confidence intervals.
• No statistically significant associations were identified for the other 14 micronutrients.
• Sensitivity analyses did not reveal substantial heterogeneity or horizontal pleiotropy.

Conclusions:

• This MR study provides preliminary genetic evidence suggesting a potential link between genetically predicted folic acid levels and RAU risk.
• The findings, particularly the nominal significance from the IVW analysis, warrant cautious interpretation due to potential limitations.
• Further research is needed to confirm these results and understand the underlying biological mechanisms, without implying direct dietary recommendations.