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Non-European ancestries remain largely underrepresented in genomic studies, and the disparity undermines genetic discovery efforts. To bridge this gap, we performed genome-wide genotyping and exome sequencing on over 140,000 participants from the Mexico City Prospective Study (MCPS) – the largest blood-based prospective study in Latin America. Leveraging these datasets in combination with whole-genome sequencing on a subset of 9,950 selected individuals, we characterised genetic variation in the cohort and identified over 31 million variants not previously reported, including 1.4 million coding variants. Identity-by-decent (IBD) estimation resolved extensive family networks and admixture analysis indicated that ancestries from Mesoamerican Indigenous populations in central, southern and south-eastern Mexico are largely represented in MCPS. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous American ancestry at exome variants, all available through a public browser. Moreover, we demonstrate that genetic variation within MCPS can improve genotype imputation and polygenic prediction in individuals of Mexican-decent. 

Dr. Jason Torres is the genetic epidemiologist lead for the Mexico City Prospective Study. He completed his PhD in Molecular Metabolism at the University of Chicago where he investigated the genetic basis of type 2 diabetes (T2D) under the supervision of Prof. Nancy Cox. As a post-doc at the Wellcome Centre for Human Genetics, Jason worked with Prof Mark McCarthy to elucidate regulatory mechanisms at fine-mapped T2D loci by integrating molecular epigenomes in human pancreatic islet cells. In 2020, Jason joined the Clinical Trials Service Unit and Epidemiological Studies Unit within Oxford Population Health (OxPop) where he leads genetic analysis of cardiometabolic traits as part of the MCPS Study Group.