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 K. Maxwell, Marcus B. Jones, Humberto Garcia‐Ortíz, Raúl Ramírez-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 D. Overton, Jeffrey G. Reid, Timothy A. Thornton, Gonçalo R. Abecasis, Jaime Berúmen, Lorena Orozco, Rory Collins, RGC Management and Leadership Team, Gonçalo R. Abecasis, Adolfo A. Ferrando, Michael Cantor, Giovanni Coppola, Andrew Deubler, Aris N. Economides, Katia Karalis, Luca A. Lotta, Lyndon J. Mitnaul, John D. Overton, Jeffrey G. Reid, Alan R. Shuldiner, Katherine Siminovitch, Sequencing and Lab Operations, Christina Beechert, Erin D. Brian, Laura M. Cremona, Hang Du, Caitlin Forsythe, Zhenhua Gu, Kristy Guevara, Michael Lattari, Alexander Lopez, Kia Manoochehri, Manasi Pradhan, Raymond Reynoso, Ricardo Schiavo, Maria Sotiropoulos Padilla, Chenggu Wang, Sarah E. Wolf, Amelia Averitt, Nilanjana Banerjee, Dadong Li, Sameer Malhotra, Justin Mower, Mudasar Sarwar, Deepika Sharma, Jeffrey Staples, Jay Sundaram, Sean Yu, Aaron Zhang, Genome Informatics and Data Engineering, Mona Nafde, George Mitra, Sujit Gokhale, Andrew Bunyea, Janice Clauer, Krishna Pawan Punuru, Sanjay Sreeram, Gisu Eom, Benjamin Sultan, Vrushali Mahajan, Eliot Austin, Koteswararao Makkena, Sean O’Keeffe, Tommy Polanco, Ayesha Rasool, William Salerno
Abstract
. 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.