Abstract
Increasing evidence shows that telomere length shortening is associated with the risk for Alzheimer’s disease (AD), pointing to a potential modifiable target for prevention. However, the causality of this association is still not clear. To investigate the causal relationship between telomere length and AD, we use two-sample Mendelian randomization (MR) to assess potential causal inference. We used summary-level data for telomere length (9,190 participants) and AD (71,880 cases and 383,378 controls). We performed two-sample MR analysis with single nucleotide polymorphisms previously identified to be associated with telomere length. The MR analyses were conducted using the inverse-variance-weighted method and complemented with the maximum likelihood, weighted median, weighted mode approaches. MR evidence suggested that shorter telomere length was causally associated with a higher risk for AD (inverse-variance weighted estimate of odds ratio (OR): 1.03 per SD decrease of telomere length, P=1.21×10−2). The maximum likelihood, weighted median, weighted mode yielded a similar pattern of effects. The results were similar in sensitivity analyses. Using genetic instruments identified from large-scale genome-wide association study, robust evidence supports a causal role of telomere length shortening with increased risk of AD.
Highlights
Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by cognitive and behavioral impairment, social and occupational dysfunction and, death
In Mendelian randomization (MR) analysis, we found evidence of a causal relationship between telomere length shortening and AD (IVW estimate of odds ratio (OR): 1.03 per 1-SD decrease in genetically determined telomere length, 95% confidence interval (CI): 1.01–1.05, P = 1.21×10−2; Figure 2 and Table 2)
Using large-scale genome-wide association study (GWAS) data for telomere length (N = 9,190) and AD data (71,880 AD cases and 383,378 controls), we performed MR analysis to assess the causal relationship between telomere length and AD using a two-sample MR analysis
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by cognitive and behavioral impairment, social and occupational dysfunction and, death. Advancing age is a major risk factor for AD, both the prevalence and global burden of AD increase with age, especially between the ages of 50 and 80 years [1]. The aetiology of AD is not well understood, it is well recognized that both environment and genetic factors are contribute to the development of AD [3]. Telomeres are shorten progressively over time during each cell division, they are recognized as physiological markers of aging [5]. Alterations of telomere length are proposed as epigenomic markers associated with a wide range of diseases, including cancer, cardiovascular diseases, neurological disorders, and psychiatric diseases [6,7,8,9,10]
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