Integrative forensic genomics resolves trace DNA in a major transnational drug trafficking case.

Illicit drug source tracing increasingly combines forensic toxicology, analytical chemistry, and genomics, yet connecting packaging or production to specific individuals remains challenging when touch DNA is limited, degraded, or contaminated. Here, we applied an integrated forensic genomics approach to a major transnational maritime cocaine trafficking case. Touch DNA recovered from multilayer packaging underwent 80 Mb SNP capture targeting autosomal, Y-chromosomal, and mitochondrial loci, with whole-genome sequencing used for comparison. Despite low DNA amounts and varying microbial contamination, the combined capture and imputation process produced usable genomic profiles for seven samples, three of which represented unique contributors. Allele-sharing analyses identified two contributors, UN01 and UN02, as closest to American reference populations, while UN03 showed a more complex profile with American, European, and African ancestries. The paternal lineages of UN01 and UN02 belonged to Q1b1a1a1, common in populations with Native American ancestry, whereas UN03 carried E1b1a1a1a2a1a3b1d1c1a, a lineage broadly linked to African ancestry. Maternal lineage inference added context, with UN03 assigned to the Native American-associated D1f and UN01/UN02 linked to deep Eurasian basal lineages. Identity-by-descent and geolocation analyses indicated stronger connections to South American reference groups for all three contributors, although the accuracy of these results was limited by uneven reference sampling and the structure of the training dataset. Overall, these findings demonstrate that combining SNP capture, genotype imputation, biogeographic ancestry inference, and phylogenetic analysis can produce valuable investigative leads from trace and degraded DNA, while also emphasizing the importance of cautious interpretation and awareness of uncertainty in forensic work.