Identification of ALS risk factors leading to CHIP-related Epi-age acceleration
Description: Most people with amyotrophic lateral sclerosis (ALS) have no family history or defined genetic risk variant. Growing evidence suggests that ALS risk factors such as military service, contact sports, traumatic brain injury, neuroinflammation, and exposure to infectious agents and industrial/environmental neurotoxins may leave a unique epigenetic footprint that can be a marker for disease, but the exact associated biological measures still need to be determined. Assessment of biological age (as opposed to the commonly used chronological age) in the blood and brain of ALS patients demonstrates that ALS patients who are older biologically experience an earlier ALS onset and a shorter disease duration. However, whether such age-acceleration is associated with risk factors previously linked to ALS is unclear. What is known is that age-acceleration is associated with a genetic condition named clonal hematopoiesis of indeterminate potential (CHIP) involving mutations in DNA regions responsible for proper gene regulation. This acquired condition associates with aging, where mutations occur in apparently healthy individuals. We hypothesize that exposure to certain risk factors leads to CHIP mutations, which in turn associates with older biological age in ALS patients. To test our hypothesis, we take advantage of our in-house already generated datasets, publicly available information, and established collaborations giving us access to a total of 10,924 samples. We calculate age-acceleration in all samples, look for mutations in 220 CHIP-associated DNA regions, and integrate respective demographic/clinical information with CHIP-related age-acceleration to uncover an ALS-specific footprint. This pilot study will allow the generation of preliminary data to secure additional funding, which in turn will allow the screening of additional patients and execution of validation experiments to develop biomarker panels and predict ALS risk factors.
Funder: ALS Association
Amount: $50,000
Funding type: award
Start date: 2023-10-01
End date: 2024-09-30
Investigator: Veronique Belzil
Institution: Mayo Clinic Jacksonville
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 24-SGP-700
OpenAlex ID: G8105711442