Mexican Biobank advances population and medical genomics of diverse ancestries

Mashaal Sohail (), María J. Palma-Martínez, Amanda Y. Chong, Consuelo D. Quinto-Cortés, Carmina Barberena-Jonas, Santiago G. Medina-Muñoz, Aaron Ragsdale, Guadalupe Delgado-Sánchez, Luis Pablo Cruz-Hervert, Leticia Ferreyra-Reyes, Elizabeth Ferreira-Guerrero, Norma Mongua-Rodríguez, Sergio Canizales-Quintero, Andrés Jimenez-Kaufmann, Hortensia Moreno-Macías, Carlos A. Aguilar-Salinas, Kathryn Auckland, Adrián Cortés, Víctor Acuña-Alonzo, Christopher R. Gignoux, Genevieve L. Wojcik, Alexander G. Ioannidis, Selene L. Fernández-Valverde, Adrian V. S. Hill, María Teresa Tusié-Luna, Alexander J. Mentzer (), John Novembre, Lourdes García-García () and Andrés Moreno-Estrada ()
Additional contact information
Mashaal Sohail: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
María J. Palma-Martínez: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
Amanda Y. Chong: University of Oxford
Consuelo D. Quinto-Cortés: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
Carmina Barberena-Jonas: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
Santiago G. Medina-Muñoz: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
Aaron Ragsdale: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
Guadalupe Delgado-Sánchez: Instituto Nacional de Salud Pública (INSP)
Luis Pablo Cruz-Hervert: Instituto Nacional de Salud Pública (INSP)
Leticia Ferreyra-Reyes: Instituto Nacional de Salud Pública (INSP)
Elizabeth Ferreira-Guerrero: Instituto Nacional de Salud Pública (INSP)
Norma Mongua-Rodríguez: Instituto Nacional de Salud Pública (INSP)
Sergio Canizales-Quintero: Instituto Nacional de Salud Pública (INSP)
Andrés Jimenez-Kaufmann: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
Hortensia Moreno-Macías: Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas UNAM/Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Carlos A. Aguilar-Salinas: Division de Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Kathryn Auckland: University of Oxford
Adrián Cortés: University of Oxford
Víctor Acuña-Alonzo: Escuela Nacional de Antropología e Historia (ENAH)
Christopher R. Gignoux: University of Colorado Anschutz Medical Campus
Genevieve L. Wojcik: Johns Hopkins Bloomberg School of Public Health
Alexander G. Ioannidis: Stanford University
Selene L. Fernández-Valverde: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)
Adrian V. S. Hill: University of Oxford
María Teresa Tusié-Luna: Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas UNAM/Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Alexander J. Mentzer: University of Oxford
John Novembre: University of Chicago
Lourdes García-García: Instituto Nacional de Salud Pública (INSP)
Andrés Moreno-Estrada: Unidad de Genómica Avanzada (UGA-LANGEBIO), Centro de Investigación y Estudios Avanzados del IPN (Cinvestav)

Nature, 2023, vol. 622, issue 7984, 775-783

Abstract: Abstract Latin America continues to be severely underrepresented in genomics research, and fine-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 over time, 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 GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.

Date: 2023
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DOI: 10.1038/s41586-023-06560-0

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