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


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.

SUBMITTER: Ziyatdinov A 

PROVIDER: S-EPMC10600010 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Ziyatdinov Andrey A   Torres Jason J   Alegre-Díaz Jesús J   Backman Joshua J   Mbatchou Joelle J   Turner Michael M   Gaynor Sheila M SM   Joseph Tyler T   Zou Yuxin Y   Liu Daren D   Wade Rachel R   Staples Jeffrey J   Panea Razvan R   Popov Alex A   Bai Xiaodong X   Balasubramanian Suganthi S   Habegger Lukas L   Lanche Rouel R   Lopez Alex A   Maxwell Evan E   Jones Marcus M   García-Ortiz Humberto H   Ramirez-Reyes Raul R   Santacruz-Benítez Rogelio R   Nag Abhishek A   Smith Katherine R KR   Damask Amy A   Lin Nan N   Paulding Charles C   Reppell Mark M   Zöllner Sebastian S   Jorgenson Eric E   Salerno William W   Petrovski Slavé S   Overton John J   Reid Jeffrey J   Thornton Timothy A TA   Abecasis Gonçalo G   Berumen Jaime J   Orozco-Orozco Lorena L   Collins Rory R   Baras Aris A   Hill Michael R MR   Emberson Jonathan R JR   Marchini Jonathan J   Kuri-Morales Pablo P   Tapia-Conyer Roberto R  

Nature 20231011 7984


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 City<sup>1</sup>. 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 America  ...[more]

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