Aim: To determine specific genetic loci that might be associated with longevity in Bulgarian population by analyzing exome pool-seq data from centenarians and a control group.

Methods: We performed whole-exome sequencing of two DNA pools, set up of 32 Bulgarian centenarians and 61 young healthy controls, respectively, and 59935 quality filtered variants were concurrently detected in both pools. Fisher’s exact test was employed to establish the significance of allele frequency difference between the pools.

Results: Forty seven variants showed significantly higher allele frequency in the centenarian compared to the control pool, and these can be considered to be positively associated with longevity in Bulgarian populaton. Based on their assigned functional role, three genes containing three of these variants were further investigated. These genes, RNF43, WNK1 and NADSYN1, are involved in evolutionary conserved processes with well ascertained association with longevity, i.e., Wnt signaling pathway, insulin/IGF-1 signal pathway and redox balancing processes, respectively. For the remaining genes exhibiting variants with significantly higher allele frequency in the Bulgarian centenarian pool there is not enough evidence about their functional role in determining longevity and further research is needed.

Conclusion: The results confirm the importance of studying centenarians in different populations to discover those combinations of variants that associate with longer health span.