Mexican Biobank advances population and medical genomics of diverse ancestries

Abstract

Latin America continuesto be severely underrepresented ingenomics research, and flne-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions overtime, unravelling Indigenous, colonial and postcolonial demographic dynamics2 6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS78. We identified genetic and environmental factors associating with trait variation, such asthe length ofthe genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into thegenetic histories of individuals in Mexico and dissectstheircomplextrait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.