Characterization of the common genetic variation in the Spanish population of Navarre

Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from those associated with disease. To this end, we conducted a comprehensive characterization of variants in the population of Navarre (Spain), utilizing whole genome sequencing data from 358 unrelated individuals of Spanish origin. Our analysis revealed 61,410 biallelic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common using a minor allele frequency (MAF) > 1%. By comparing allele frequency data from 1000 Genome Project Phase 3 (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort including IBS individuals as well as data from Medical Genome Project, we identified 1,069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. This observation was further corroborated by a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1,069 SNVs as common in Navarre. In conclusion, this study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement NAGEN1,000 and PharmaNAGEN were supported by Navarra Gov (Direccion General de Industria, Energia y Proyectos Estrategicos S3). GRANTS_NUMBERS: 0011-1411-2017-000032, 0011-1411-2018-000047. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: NAGEN1,000 and PharmaNAGEN were approved by Navarra Ethics Committee for Clinical Research (CEIC Navarra). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author upon reasonable request.