Identification of genetic variations associated with neurodegenerative diseases using clinical exome Next-Generation Sequencing in older adults from Panama.

Neurodegenerative diseases (ND) represent a growing worldwide problem due to the increase in population aging that is advancing rapidly and where age is the most recognized risk factor for the development of multiple ND. Population aging is occurring more rapidly in low- and middle-income countries, such as Panama, making it a priority for the country to identify genetic factors associated with these conditions at an early stage, which is necessary information for the development of effective preventive and therapeutic strategies. The objective of this study was to identify genetic variants related to ND in older adults in Panama. A total of 44 DNA samples from participants ≥ 50 years recruited in the community by the Panama Aging Research Initiative-Health Disparities (PARI-HD) were analyzed by massive sequencing using clinical exome. The data obtained were analyzed using a customized virtual panel for the identification of variants in 138 genes related to ND. A total of 294 genetic variants were identified, 73.9% being benign, 20.7% variants of uncertain significance (VUS), 3.4% probably pathogenic and 2.0% pathogenic. Presenting variants such as CR1 and TREM2 related to Alzheimer's disease, PRKN, NEFH and GIGYF2 related to Parkinson's disease, HLA-DRB1 with multiple sclerosis, amyotrophic lateral sclerosis and GRN variant related to frontotemporal dementia. This study establishes the basis for a better understanding of genetic risk factors in our population, and is conducive to the integration of massive sequencing as a tool for the personalization of the clinical management of these pathologies.