Association between Dried Fruit Intake and DNA Methylation: A Multivariable Mendelian Randomization Analysis.

Area of Science:

• Epigenetics
• Nutritional Epidemiology
• Genetics

Background:

• Observational studies suggest a link between dried fruit consumption and DNA methylation (DNAm).
• However, observational designs are prone to confounding and reverse causality, questioning the causal nature of this association.

Purpose of the Study:

• To investigate the causal relationship between dried fruit intake and DNA methylation using Mendelian randomization.
• To assess the impact of dried fruit consumption on epigenetic aging markers.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis utilizing the IEU Open GWAS database.
• Selection of 43 single nucleotide polymorphisms (SNPs) associated with dried fruit intake as instrumental variables.
• Analysis of DNAm outcomes including GrimAge acceleration (AgeAccelGrim) and PhenoAge acceleration (AgeAccelPheno), with sensitivity analyses performed using MR-Egger and weighted median methods.

Main Results:

• Dried fruit intake showed a statistically significant association with lower AgeAccelGrim (β=-1.365, P=2.985×10-3) and AgeAccelPheno (β=-1.933, P=8.371×10-4).
• Multivariable MR confirmed these causal effects, with adjusted estimates for AgeAccelGrim (β=-1.315, P=1.480×10-2) and AgeAccelPheno (β=-1.595, P=2.483×10-2).
• No significant associations were found for other DNAm markers, and sensitivity analyses indicated no substantial horizontal pleiotropy.

Conclusions:

• This MR study provides evidence that increased dried fruit intake causally reduces GrimAge and PhenoAge acceleration.
• These findings suggest a potential role for dried fruits in promoting healthier aging and potentially extending lifespan.