Isonymy and inbreeding in Boyacá, Colombia: Implications for rare disease risk

Abstract

The frequency of rare and orphan genetic diseases is high in some populations in the Colombian department of Boyacá. This is arguably associated with the elevated consanguinity in the region, which can increase autozygosity and the expression of recessive conditions. Surname sharing (Isonymy) analysis is useful for evaluating consanguinity, population migration patterns, and population structure. Here, we estimated inbreeding-related parameters via isonymy analysis to characterize the population structure of Boyacá and to assess whether population isolation is consistent with increased risk of rare genetic diseases in the region. Data were retrieved from national databases, such as the System of Potential Beneficiaries of Social Programs (SISBÉN) and the National Public Health Surveillance System (SIVIGILA). We also obtained information from a demographic and genealogical survey conducted with 1 033 participants in the department of Boyacá. Based on SISBÉN data, isonymy parameters were calculated to assess population isolation and relatedness, while reports of genetic diseases from SIVIGILA were analyzed to explore their relationship with kinship coefficients. This was complemented by genealogical surveys, principal coordinates analysis (PCoA), and cluster analysis. The highest kinship coefficients were found in the municipalities of Chíquiza and Pisba, and no correlation was found between the kinship coefficient and the municipality-level distribution of reported genetic disease cases. Overall, the isonymy parameters were comparable to those reported in population isolates, highlighting the presence of genetically isolated subpopulations in Boyacá. Such isolation is likely consistent with founder effects and local enrichment of rare variants. However, confirmation of a relationship with rare disease risk requires targeted genetic studies and improved epidemiological surveillance.