Telomere Length Shortening in Alzheimer's Disease: Procedures for a Causal Investigation Using Single Nucleotide Polymorphisms in a Mendelian Randomization Study.

Measuring the length of telomeres, repetitive nucleotide sequences capping the chromosomes which shortens by each cell division, has become a popular way of attaining a marker of biological aging processes. Several observational studies have investigated the associations between telomere length and Alzheimer's disease (AD) with the overall conclusion being shorter telomeres provide an increased risk for AD development. Here we present an alternative approach for addressing the topic where additional evidence on causality can be drawn. To do so, we include information on single nucleotide polymorphisms (SNPs) using nature's own experiment with random segregation of alleles at conception. The protocol describes the full process of the so-called Mendelian Randomization by selecting appropriate SNPs for the analysis, discussing different data sources that can be used and inform about methods, assumptions and suitable software packages including Stata code.