Association between telomere length and idiopathic normal pressure hydrocephalus: a Mendelian randomization study

Area of Science:

• Genetics
• Aging
• Neurology

Background:

• Idiopathic normal pressure hydrocephalus (iNPH) is common in older adults.
• Telomere length is a marker of biological aging.
• The relationship between telomere length and iNPH requires further investigation.

Purpose of the Study:

• To investigate the association between telomere length and iNPH using Mendelian randomization (MR).
• To explore potential underlying mechanisms, including vascular risk factors.

Main Methods:

• Utilized genetic variants for telomere length from UK Biobank (n=472,174).
• Acquired iNPH summary data from the FinnGen consortium (n=218,365).
• Employed five MR estimation methods and conducted sensitivity analyses, including multivariable MR.

Main Results:

• Genetically determined longer telomere length showed a significant inverse association with iNPH risk (OR=0.44, p=0.008).
• Sensitivity analyses indicated no significant heterogeneity or pleiotropy.
• Multivariable MR suggested attenuation of the association after adjusting for hypertension, type 2 diabetes, and coronary artery disease.

Conclusions:

• A strong negative correlation exists between telomere length and iNPH.
• Vascular risk factors may mediate the causal relationship between telomere length and iNPH.