Coancestry-based analysis of inbreeding in worldwide human populations

Introduction: This study reports on a coancestry-based analysis of inbreeding in worldwide human populations. It employs 15 hypervariable autosomal short tandem repeat (STR) loci included in the AmpFlSTR PCR amplification kit in combination with the EMIBD9 program to assess levels of inbreeding in worldwide human populations with different biogeographical and cultural characteristics. It provides the first large-scale, systematic validation of the EMIBD9 framework for quantifying inbreeding in small, structured human populations. Materials and methods: The r ^ EM1 option of the EMIBD9 program was used to ascertain levels of inbreeding in 58 globally distributed populations of different sizes. The r ^ EM1 option is an expectation maximization (EM) platform that corrects allelic frequency during the run and is specifically designed to assess levels of inbreeding in skewed, limited-size population databases. Results: Populations were partitioned into four statistically significant clusters reflecting levels of inbreeding. Cluster 1, which includes populations with the lowest inbreeding levels, is mostly made up of putatively outbred populations while the other three clusters (i.e., 2, 3, and 4) are made up of populations with increasing levels of inbreeding. The partitioning was supported by statistically significant values when the Mann–Whitney U test was applied individually to the coancestry (p < 0.001) and F (p < 0.001) values. The data presented in this article suggest a wide spectrum of inbreeding levels rather than a simple inbred/outbred dichotomy among human groups and underscores the need for a systematic assessment of inbreeding especially in understudied communities. Pockets of distinct levels of inbreeding within populations suggest that subpopulation genetic heterogeneity exists in which portions of some populations may practice different levels of inbreeding. Conclusions: The data presented in this article suggest a wide spectrum of inbreeding levels among human groups and underscores the need for a systematic assessment of inbreeding in understudied communities. Although the STR system presented in this study cannot outperform genome-wide single nucleotide polymorphism (SNP) data of whole genome sequencing (WGS) to perform runs of homozygosity for assessing inbreeding, it shows that STRs remain a valuable method for low-resource settings and a large number of individuals.