Expanding CIRdb, a comprehensive catalog of whole-exome sequencing data of Canary Islanders.

The Canary Islanders exhibit a unique genetic admixture, comprising European (EUR), North African (NAF), and sub-Saharan African (SSA) ancestries. We comprehensively characterized the full spectrum of small genetic variation in this population based on whole-exome sequencing data to further develop CIRdb. Our results revealed 387,555 variants, of which 15.1% were previously unreported, and we prioritized novel putative pathogenic variants exhibiting enrichment in respiratory, cardiovascular, and metabolic disorders. Genetic differentiation patterns provided fine-grained insights into within-archipelago differentiation. We revealed an EUR genetic ancestry enrichment around the 17q21.31 inversion (a pleiotropic locus associated with pulmonary, infectious, and immunological diseases) and a candidate selective sweep shared by Canary Islanders and the NAF population around prune exopolyphosphatase 1 (PRUNE1) gene, which is associated with body mass index, cardiovascular health, and metabolic and respiratory traits. Taken together, our findings show that CIRdb presents a valuable resource of exome-wide genetic variation in a population at the edge of Southwestern European genetic diversity.