Is He Really My Relative? Kinship Cases in Substructured Populations: A Study on the Lebanese Population

Probabilistic analysis performed in DNA kinship cases is affected by factors such as the number of loci analyzed, STR allelic relative frequency dataset, and population genetic characteristics of individuals involved in the analysis. The Lebanese population shows high rates of endogamy and consanguinity, which could challenge the power of discrimination of DNA profiles and be a source of misleading conclusions. The present study aims at evaluating the probability of false positives in relationship testing, especially siblingships, avuncular, and grandparent-grandchildren relationship, when cases are subject to different constraints as of DNA profile size (15 vs 23 STR loci), and inbreeding coefficients (Fst). 126 790 kinship comparisons were performed for each of the stated types of kinship tests using a Lebanese database of 505 unrelated heathy individuals. To do so, the DNA of unrelated individuals was analyzed and the results were assessed under a pair of propositions involving the stated relative/not relative links between the two individuals, offering a quantification through the likelihood ratio (LR)–a widely accepted metrics to assess the value of scientific results. 1995 (1.6%) simulated cases showed false associations for full sibship relations when the DNA profile size used was of 15 STRs (LR greater than 1, or log(LR) greater than 0). False associations decreased to 340 (0.3%) cases when the DNA profile size was increased to 23 STRs, and to 299 (0.2%) and 91 (0.07%) cases, when coancestry coefficient for the Lebanese population (0.002) and those recommended by the National Research Committee (0.02) were adopted, respectively. The simulations of half siblingships (which represent the half sib-ships, avuncular, and grandparent-grandchildren relationships) showed similar results. Conversely, 41 full biological siblingships cases, 24 true full siblingship laboratory cases, and 124 true half siblingships laboratory cases, were used as controls to assess the effect of implementing the conditions previously applied on the simulations (profile size and Fst values) to lower false associations. Results for the positive controls showed that the implementation of NRC recommended Fst value of 0.02 decreased the likelihood ratio by an average of 102 for DNA profiles with 15 STRs, and by an average of 104 with DNA profiles of 23 STRs, which did not lead to misleading results. However, the use of a DNA profile size of 23 STRs with the Lebanese coancestry coefficients showed the most meaningful results. This study could help set national recommendations for the interpretation of kinship testing in the Lebanese population.