The effect of micronutrient levels on leukocyte telomere length: A Mendelian randomization study

Leukocyte telomeres play a crucial role in maintaining genomic stability and human health. This study used Mendelian randomization (MR) to investigate the effects of vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, calcium, carotenoids, copper, folate, iron, magnesium, potassium, selenium, and zinc on leukocyte telomere length (LTL). Summary statistics were obtained from genome-wide association studies for both exposure and outcome data. This study performed MR analysis on each exposure-outcome pair. The weighted median, MR-Egger, and MR-PRESSO methods were used for performing sensitivity analyses. The MR-Egger regression intercept was employed for assessing directional pleiotropy, and the MR-PRESSO test for analyzing individual outliers due to pleiotropic effects. The inverse-variance weighted method is our primary estimation tool. Univariable MR analyses identified potential associations between genetically predicted copper and vitamin B6 levels and LTL. However, multivariable Mendelian randomization analysis revealed that only copper retained a significant positive causal effect on LTL (P < .05), whereas the association with vitamin B6 was attenuated and became non-significant after adjustment. This study provides genetic evidence consistent with an association between higher copper levels and longer LTL. While vitamin B6 showed a nominal association in univariable analysis, it was not an independent predictor in the multivariable model. These findings highlight a potential role of copper in telomere biology, although further mechanistic studies are warranted to validate these results.