PT  - JOURNAL ARTICLE
AU  - Andrey Ziyatdinov
AU  - Jason Torres
AU  - Jesús Alegre-Díaz
AU  - Joshua Backman
AU  - Joelle Mbatchou
AU  - Michael Turner
AU  - Sheila M. Gaynor
AU  - Tyler Joseph
AU  - Yuxin Zou
AU  - Daren Liu
AU  - Rachel Wade
AU  - Jeffrey Staples
AU  - Razvan Panea
AU  - Alex Popov
AU  - Xiaodong Bai
AU  - Suganthi Balasubramanian
AU  - Lukas Habegger
AU  - Rouel Lanche
AU  - Alex Lopez
AU  - Evan Maxwell
AU  - Marcus Jones
AU  - Humberto García-Ortiz
AU  - Raul Ramirez-Reyes
AU  - Rogelio Santacruz-Benítez
AU  - Abhishek Nag
AU  - Katherine R. Smith
AU  - Regeneron Genetics Center
AU  - Mark Reppell
AU  - Sebastian Zöllner
AU  - Eric Jorgenson
AU  - William Salerno
AU  - Slavé Petrovski
AU  - John Overton
AU  - Jeffrey Reid
AU  - Timothy Thornton
AU  - Goncalo Abecasis
AU  - Jaime Berumen
AU  - Lorena Orozco-Orozco
AU  - Rory Collins
AU  - Aris Baras
AU  - Michael R Hill
AU  - Jonathan R Emberson
AU  - Jonathan Marchini
AU  - Pablo Kuri-Morales
AU  - Roberto Tapia-Conyer
TI  - Genotyping, sequencing and analysis of 140,000 adults from the Mexico City Prospective Study
AID  - 10.1101/2022.06.26.495014
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.26.495014
4099  - http://biorxiv.org/content/early/2022/06/29/2022.06.26.495014.short
4100  - http://biorxiv.org/content/early/2022/06/29/2022.06.26.495014.full
AB  - The Mexico City Prospective Study (MCPS) is a prospective cohort of over 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City. We generated genotype and exome sequencing data for all individuals, and whole genome sequencing for 10,000 selected individuals. We uncovered high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Native American, European and African ancestry, with extensive admixture from indigenous groups in Central, Southern and South Eastern Mexico. Native 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 population specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Native Mexico at exome variants, all available via a public browser. Using whole genome sequencing, we developed an imputation reference panel which outperforms existing panels at common variants in individuals with high proportions of Central, South and South Eastern Native Mexican ancestry. Our work illustrates the value of genetic studies in populations with diverse ancestry 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.Competing Interest StatementAndrey Ziyatdinov, Joshua Backman, Joelle Mbatchou, Sheila M. Gaynor, Tyler Joseph, Yuxin Zou, Daren Liu, Jeffrey Staples, Razvan Panea, Xiaodong Bai, Suganthi Balasubramanian, Lukas Habegger, Rouel Lanche, Alex Lopez, Evan Maxwell, Marcus Jones, Eric Jorgenson, William Salerno, John Overton, Jeffrey Reid, Timothy Thornton, Goncalo Abecasis, Aris Baras, Jonathan Marchini are current employees and/or stockholders of Regeneron Genetics Center or Regeneron Pharmaceuticals. Abhishek Nag, Katherine Smith and Slave Petrovski are current employees and/or stockholders of AstraZeneca Mark Reppell is current employee and/or stockholder of AbbVie.