Telomere Length Shortening and Alzheimer Disease—A Mendelian Randomization Study

Telomeres are sequences of repetitive nucleotides at the end of the chromosomes, which protect them from fusion with neighboring chromosomes. 1 Observational studies have found associations between shorter telomeres and Alzheimer disease (AD). 2 However, these studies could have residual confounding or reverse causation, making it difficult to draw conclusions on whether telomere length (TL) is causally associated with AD. For the past decades, instrumental variable (IV) analysis has been developed for assessing causality using genetic variants in epidemiological research under the name of mendelian randomization (MR). 3 In the present study, we investigated the causal effect of TL on AD by applying the MR method to summary genome-wide association study (GWAS) data from Codd et al 4 and from the International Genomics of Alzheimer's Project Consortium.