Nationwide genomic biobank in Mexico unravels demographic history and complex trait architecture from 6,057 individuals

Abstract

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories as well as complex trait architectures remain hidden due to the lack of Big Data. To fill this gap, the Mexican Biobank project genotyped 1.8 million markers in 6,057 individuals from 32 states and 898 sampling localities across Mexico with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Through a suite of state-of-the-art methods for ancestry deconvolution and inference of identity-by-descent (IBD) segments, we inferred detailed ancestral histories for the last 200 generations in different Mesoamerican regions, unraveling native and colonial/post-colonial demographic dynamics. We observed large variations in runs of homozygosity (ROH) among genomic regions with different ancestral origins reflecting their demographic histories, which also affect the distribution of rare deleterious variants across Mexico. We analyzed a range of biomedical complex traits and identified significant genetic and environmental factors explaining their variation, such as ROH found to be significant predictors for trait variation in BMI and triglycerides. 2 bioRxiv preprint doi: https://doi.org/10.1101/2022.07.11.499652; this version posted July 14, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 The genetic architecture of complex traits in admixed genomes cannot be understood outside the context of their underlying histories. Present-day Mexico covers seven Mesoamerican regions with rich civilizational histories . Archaeology and anthropology regionalize Mexico into the north of Mexico, the north of Mesoamerica, the center, occident and gulf of Mexico, Oaxaca and the Mayan region (Fig. 1a). These are based on noting specific pre-Hispanic civilizations and cultures, which began flourishing very early in the Mayan region, in Oaxaca, in the occident and in the gulf of Mexico , and later in the center and north of Mesoamerica. …