Telomere length is causally connected to brain MRI image derived phenotypes: A mendelian randomization study

Area of Science:

• Neuroimaging
• Genetics
• Aging Research

Background:

• Shorter telomere length (TL) is associated with neurodegenerative diseases and aging.
• The causal link between TL and brain characteristics (image-derived phenotypes, IDPs) is not fully understood.

Purpose of the Study:

• To investigate the causal relationship between TL and a comprehensive set of brain IDPs using Mendelian randomization.
• To explore the impact of TL on white matter integrity and its potential role in brain age estimation.

Main Methods:

• Utilized two-sample Mendelian randomization (MR).
• Analyzed associations between genetic variants for TL and 3,935 brain IDPs derived from MRI.
• Examined associations with diffusion metrics, including fractional anisotropy and diffusivity measures.

Main Results:

• Identified significant causal associations between TL and 193 brain IDPs.
• Found that longer TL was associated with decreased fractional anisotropy and increased axial, radial, and mean diffusivity in white matter tracts.
• Observed associations with IDPs previously linked to brain age estimation, though effect directions differed from aging effects.

Conclusions:

• Telomere length plays a causal role in determining white matter integrity.
• Findings highlight TL as a significant factor influencing brain structure and potentially brain age.
• The relationship between TL and brain IDPs warrants further investigation in the context of aging and neurological health.