TY - JOUR
T1 - Genotyping, sequencing and analysis of 140,000 adults from Mexico City
AU - Research Program Management and Strategic Initiatives
AU - Mexico City Prospective Study
AU - Field transportation
AU - Genetics and bioinformatics
AU - Laboratory operations
AU - Regeneron Genetics Center
AU - RGC Management and Leadership Team
AU - Sequencing and Lab Operations
AU - Clinical Informatics
AU - Genome Informatics and Data Engineering
AU - Analytical Genetics and Data Science
AU - Therapeutic Area Genetics
AU - Ziyatdinov, Andrey
AU - Torres, Jason
AU - Alegre-Díaz, Jesús
AU - Backman, Joshua
AU - Mbatchou, Joelle
AU - Turner, Michael
AU - Gaynor, Sheila M.
AU - Joseph, Tyler
AU - Zou, Yuxin
AU - Liu, Daren
AU - Wade, Rachel
AU - Staples, Jeffrey
AU - Panea, Razvan
AU - Popov, Alex
AU - Bai, Xiaodong
AU - Balasubramanian, Suganthi
AU - Habegger, Lukas
AU - Lanche, Rouel
AU - Lopez, Alex
AU - Maxwell, Evan
AU - Jones, Marcus
AU - García-Ortiz, Humberto
AU - Ramirez-Reyes, Raul
AU - Santacruz-Benítez, Rogelio
AU - Nag, Abhishek
AU - Smith, Katherine R.
AU - Damask, Amy
AU - Lin, Nan
AU - Paulding, Charles
AU - Reppell, Mark
AU - Zöllner, Sebastian
AU - Jorgenson, Eric
AU - Salerno, William
AU - Petrovski, Slavé
AU - Overton, John
AU - Reid, Jeffrey
AU - Thornton, Timothy A.
AU - Abecasis, Gonçalo
AU - Berumen, Jaime
AU - Orozco-Orozco, Lorena
AU - Collins, Rory
AU - Ferrando, Adolfo
AU - Cantor, Michael
AU - Coppola, Giovanni
AU - Deubler, Andrew
AU - Economides, Aris
AU - Karalis, Katia
AU - Lotta, Luca A.
AU - Mitnaul, Lyndon J.
AU - Vrieze, Scott
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/10/26
Y1 - 2023/10/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85173802215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85173802215&partnerID=8YFLogxK
U2 - 10.1038/s41586-023-06595-3
DO - 10.1038/s41586-023-06595-3
M3 - Article
C2 - 37821707
AN - SCOPUS:85173802215
SN - 0028-0836
VL - 622
SP - 784
EP - 793
JO - Nature
JF - Nature
IS - 7984
ER -