Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD) Project, compiling genome-wide information from 53,738 Latin Americans across 39 studies representing 46 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene flow across the Americas. Additionally, we developed GLAD-match, a simulated annealing-based algorithm, to match the genetic background of external samples to our database, sharing summary statistics (i.e., allele and haplotype frequencies) without transferring individual-level genotypes. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic software in the presence of admixture. By providing this resource, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people

Strong positive selection biases identity-by-descent-based inferences of recent demography and population structure in Plasmodium falciparum

Funding Information: We would like to thank the participants in studies contributing clinical samples from which the parasite WGS data were generated, as well as the clinical investigators at the Armed Forces Research Institute of Medical Sciences who conducted the studies contributing parasite isolates to our in-house data set. This publication uses data from the MalariaGEN Consortium and Plasmodium falciparum Community Project as described in “An open data set of Plasmodium falciparum genome variation in 7000 worldwide samples. MalariaGEN et al., Wellcome Open Research 2021642 DOI: 10.12688/wellcomeopenres.16168.1.” This work was supported by NIH 1R01AI145852 granted to ST-H and TDO by the U.S. National Institutes of Health. Publisher Copyright: © The Author(s) 2024.Malaria genomic surveillance often estimates parasite genetic relatedness using metrics such as Identity-By-Decent (IBD), yet strong positive selection stemming from antimalarial drug resistance or other interventions may bias IBD-based estimates. In this study, we use simulations, a true IBD inference algorithm, and empirical data sets from different malaria transmission settings to investigate the extent of this bias and explore potential correction strategies. We analyze whole genome sequence data generated from 640 new and 3089 publicly available Plasmodium falciparum clinical isolates. We demonstrate that positive selection distorts IBD distributions, leading to underestimated effective population size and blurred population structure. Additionally, we discover that the removal of IBD peak regions partially restores the accuracy of IBD-based inferences, with this effect contingent on the population’s background genetic relatedness and extent of inbreeding. Consequently, we advocate for selection correction for parasite populations undergoing strong, recent positive selection, particularly in high malaria transmission settings.publishersversionpublishe

Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD) Project, compiling genome-wide information from 53,738 Latin Americans across 39 studies representing 46 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene flow across the Americas. Additionally, we developed GLAD-match, a simulated annealing-based algorithm, to match the genetic background of external samples to our database, sharing statistics (i.e., allele and haplotype frequencies) without transferring individual-level genotypes. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic software in the presence of admixture. By providing this resource, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people

Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD) Project, compiling genome-wide information from 53,738 Latin Americans across 39 studies representing 46 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene flow across the Americas. Additionally, we developed GLAD-match, a simulated annealing-based algorithm, to match the genetic background of external samples to our database, sharing summary statistics (i.e., allele and haplotype frequencies) without transferring individual-level genotypes. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic software in the presence of admixture. By providing this resource, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people. [Display omitted] •We present GLADdb, a collection of 53,000 Latin American individuals•We identified ancestry-biased migration across the Americas•We present GLAD-match to identify similarities without sharing individual genotypes•GLADdb is a valuable resource for evaluating genetic epidemiology software In this article, Borda, Loech, Guo, and Laboulaye et al. developed the Genetics of Latin American Diversity database (GLADdb), which includes 53,000 Latin Americans. With GLADdb, they explored two gaps in Latino genomics: (1) population structure and recent gene flow and (2) the underrepresentation of Latinos in genetic epidemiology