Genotyping, sequencing and analysis of 140,000 adults from Mexico City

Andrey Ziyatdinov, Jason Torres (), Jesús Alegre-Díaz, Joshua Backman, Joelle Mbatchou, Michael Turner, Sheila M. Gaynor, Tyler Joseph, Yuxin Zou, Daren Liu, Rachel Wade, Jeffrey Staples, Razvan Panea, Alex Popov, Xiaodong Bai, Suganthi Balasubramanian, Lukas Habegger, Rouel Lanche, Alex Lopez, Evan Maxwell, Marcus Jones, Humberto García-Ortiz, Raul Ramirez-Reyes, Rogelio Santacruz-Benítez, Abhishek Nag, Katherine R. Smith, Amy Damask, Nan Lin, Charles Paulding, Mark Reppell, Sebastian Zöllner, Eric Jorgenson, William Salerno, Slavé Petrovski, John Overton, Jeffrey Reid, Timothy A. Thornton, Gonçalo Abecasis, Jaime Berumen, Lorena Orozco-Orozco, Rory Collins, Aris Baras, Michael R. Hill, Jonathan R. Emberson, Jonathan Marchini (), Pablo Kuri-Morales and Roberto Tapia-Conyer ()
Additional contact information
Andrey Ziyatdinov: Regeneron Genetics Center
Jason Torres: University of Oxford
Jesús Alegre-Díaz: National Autonomous University of Mexico (UNAM)
Joshua Backman: Regeneron Genetics Center
Joelle Mbatchou: Regeneron Genetics Center
Michael Turner: University of Oxford
Sheila M. Gaynor: Regeneron Genetics Center
Tyler Joseph: Regeneron Genetics Center
Yuxin Zou: Regeneron Genetics Center
Daren Liu: Regeneron Genetics Center
Rachel Wade: University of Oxford
Jeffrey Staples: Regeneron Genetics Center
Razvan Panea: Regeneron Genetics Center
Alex Popov: Regeneron Genetics Center
Xiaodong Bai: Regeneron Genetics Center
Suganthi Balasubramanian: Regeneron Genetics Center
Lukas Habegger: Regeneron Genetics Center
Rouel Lanche: Regeneron Genetics Center
Alex Lopez: Regeneron Genetics Center
Evan Maxwell: Regeneron Genetics Center
Marcus Jones: Regeneron Genetics Center
Humberto García-Ortiz: Instituto Nacional de Medicina Genómica, Tlalpan
Raul Ramirez-Reyes: National Autonomous University of Mexico (UNAM)
Rogelio Santacruz-Benítez: National Autonomous University of Mexico (UNAM)
Abhishek Nag: AstraZeneca
Katherine R. Smith: AstraZeneca
Amy Damask: Regeneron Genetics Center
Nan Lin: Regeneron Genetics Center
Charles Paulding: Regeneron Genetics Center
Mark Reppell: AbbVie
Sebastian Zöllner: University of Michigan
Eric Jorgenson: Regeneron Genetics Center
William Salerno: Regeneron Genetics Center
Slavé Petrovski: AstraZeneca
John Overton: Regeneron Genetics Center
Jeffrey Reid: Regeneron Genetics Center
Timothy A. Thornton: Regeneron Genetics Center
Gonçalo Abecasis: Regeneron Genetics Center
Jaime Berumen: National Autonomous University of Mexico (UNAM)
Lorena Orozco-Orozco: Instituto Nacional de Medicina Genómica, Tlalpan
Rory Collins: University of Oxford
Aris Baras: Regeneron Genetics Center
Michael R. Hill: University of Oxford
Jonathan R. Emberson: University of Oxford
Jonathan Marchini: Regeneron Genetics Center
Pablo Kuri-Morales: Instituto Tecnológico y de Estudios Superiores de Monterrey
Roberto Tapia-Conyer: National Autonomous University of Mexico

Nature, 2023, vol. 622, issue 7984, 784-793

Abstract: Abstract The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.

Date: 2023
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DOI: 10.1038/s41586-023-06595-3

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