Genotyping, sequencing and analysis of 140,000 adults from Mexico City
Authors: Ziyatdinov Andrey , Torres Jason , Alegre-Díaz Jesús , Backman Joshua , Mbatchou Joelle , Turner Michael , Gaynor Sheila M. , Joseph Tyler , Zou Yuxin , Liu Daren , Wade Rachel , Staples Jeffrey , Panea Razvan , Popov Alex , Bai Xiaodong , Balasubramanian Suganthi , Habegger Lukas , Lanche Rouel , Lopez Alex , Maxwell Evan , Jones Marcus , García-Ortiz Humberto , Ramirez-Reyes Raul , Santacruz-Benítez Rogelio , Nag Abhishek , Smith Katherine R. , Damask Amy , Lin Nan , Paulding Charles , Reppell Mark , Zöllner Sebastian , Jorgenson Eric , Salerno William , Petrovski Slavé , Overton John , Reid Jeffrey , Thornton Timothy A. , Abecasis Gonçalo , Berumen Jaime , Orozco-Orozco Lorena , Collins Rory ,   Regeneron Genetics Center,   RGC Management and Leadership Team, Abecasis Gonçalo , Ferrando Adolfo , Cantor Michael , Coppola Giovanni , Deubler Andrew , Economides Aris , Karalis Katia , Lotta Luca A. , Mitnaul Lyndon J. , Overton John D. , Reid Jeffrey G. , Shuldiner Alan , Siminovitch Katherine ,   Sequencing and Lab Operations, Beechert Christina , Brian Erin D. , Cremona Laura M. , Du Hang , Forsythe Caitlin , Gu Zhenhua , Guevara Kristy , Lattari Michael , Lopez Alexander , Manoochehri Kia , Pradhan Manasi , Reynoso Raymond , Schiavo Ricardo , Padilla Maria Sotiropoulos , Wang Chenggu , Wolf Sarah E. ,   Clinical Informatics, Averitt Amelia , Banerjee Nilanjana , Li Dadong , Malhotra Sameer , Mower Justin , Sarwar Mudasar , Sharma Deepika , Staples Jeffrey C. , Sundaram Jay , Yu Sean , Zhang Aaron ,   Genome Informatics and Data Engineering, Nafde Mona , Mitra George , Gokhale Sujit , Bunyea Andrew , Clauer Janice , Punuru Krishna Pawan , Sreeram Sanjay , Eom Gisu , Sultan Benjamin , Mahajan Vrushali , Austin Eliot , Makkena Koteswararao , O’Keeffe Sean , Polanco Tommy , Rasool Ayesha , Salerno William J. , Zhang Lance , Boutkov Boris , Edelstein Evan , Gorovits Alexander , Guan Ju , Hawes Alicia , Krasheninina Olga , Mansfield Adam J. , Maxwell Evan K. , Bao Suying , Sun Kathie , Zhang Chuanyi ,   Analytical Genetics and Data Science, Ferreira Manuel Allen Revez , Burch Kathy , Campos Adrian , Chen Lei , Choi Sam , Ganel Liron , Gaynor Sheila , Geraghty Benjamin , Ghosh Akropravo , Martinez Salvador Romero , Gillies Christopher , Gurski Lauren , Herman Joseph , Kessler Michael , Kosmicki Jack , Locke Adam , Nakka Priyanka , Marcketta Anthony , Moscati Arden , Pandey Aditeya , Pandit Anita , Ross Jonathan , Sidore Carlo , Stahl Eli , Suciu Maria , VandeHaar Peter , Vedantam Sailaja , Vrieze Scott , Wang Rujin , Wu Kuan-Han , Ye Bin , Zhang Blair , Delaneau Olivier , Ghoussaini Maya , Zhang Jingning ,   Therapeutic Area Genetics, Hobbs Brian , Silver Jon , Palmer William , Guerreiro Rita , Freudenberg Jan , Joshi Amit , Baldassari Antoine , Willer Cristen , Graham Sarah , Nielsen Jonas Bille , Hass Mary , Verweij Niek , Hindy George , Bovijn Jonas , De Tanima , Akbari Parsa , Sun Luanluan , Sosina Olukayode , Gilly Arthur , Dornbos Peter , Rodriguez-Flores Juan , Riaz Moeen , Kapoor Manav , Tzoneva Gannie , Jallow Momodou W. , Alkelai Anna , Ayer Ariane , Rajagopal Veera , Gelfman Sahar , Kumar Vijay , Otto Jacqueline , Parikshak Neel , Guvenek Aysegul , Bras Jose , Alvarez Silvia , Brown Jessie , He Jin , Khiabanian Hossein ,   Research Program Management and Strategic Initiatives, Jones Marcus B. , Chen Esteban , Hernandez Jaimee , LeBlanc Michelle G. , Mighty Jason , Nishtala Nirupama , Rana Nadia , Rico-Varela Jennifer ,   Mexico City Prospective Study,   Principal investigators Mexico,   Principal investigators Oxford, Emberson Jonathan R. , Peto Richard ,   Data collection, Garduño-Martinez Abraham , Garcia-Lopez Abril , Abarca-Cardoso Adrian , Caballero-Mondragon Adriana , Gutierrez-Parra Adriana , Diaz-Avila Adriana Leticia , Bautista-Hernandez Alan Emiliano , Méndez-Villalba Alberto , Ramos-Hernandez Aldo Shaid , Alejo-Salazar Alejandra , Perez-Moncada Alejandra Angelica , Martinez Alejandra , Peralta-Gallardo Alejandra , Flores-Magana Alejandro , Benitez-Garcia Alfa Izamar , González-Castillo Alicia , Villegas-Esparza Alicia , Morales-Bravo Alma Delia , Mora-Negrete Alma Fernanda , Hernandez-Galicia Alma , Arenas-García Alma Rosa , Valentin-Martinez Alma Rosa , Paredes-Rojas Amalia , Flores-Sanchez Ambar Nayeli , Ortiz-Jaen Amelia , Juarez-Salazar America , Cervantes-Torres América Victoria , Luviano-Martínez Amparo , del Carmen Alejandro-Perez Ana , Dominguez-Alvarado Ana , Fuentes-Alvarado Ana Isabel , Arreola-Olvera Ana Karen , Bautista-Sanchez Ana Laura , Enríquez-Álvarez Ana Lilia , Reynoso-Valverde Ana Lilia , Isidro-Cid Ana María , Lechuga-Mendoza Ana Montserrat , Esquivel-Mejía Andrea , Galvino-Antonio Andrea , Gomez-Luna Andrea , Martinez-Martinez Andres , Aragón-Domínguez Anel , Gamboa-Romero Angelica , Guerrero Angelica , Ruiz-Hernandez Angelica , González-María Antonia , Martínez-Santana Araceli , Rojas-Vásquez Araceli , Rojas-Santamaría Arcelia , Sánchez-Corral Armida , Rosas-Avila Athzin Berenice , Cruz-Acevedo Beatriz , Gonzalez-Ibañes Beatriz , Rojas Beatriz , Velázquez-Mancilla Beatriz , Escalona-Franco Belen , Ochoa-Morales Bernardo , Rivera-Cortés Braulio , Castañeda-Gazpar Brenda , Calderon-Garcia Brenda J. , Jimenez-Gutierrez Brenda Jimena , Sanchez-Martin Brian Orlando , Toxqui-Rico Carlos Alberto , Clemente-Montano Carlos Antonio , Jimenez-Gutierrez Carlos Daniel , Alvarez-Meneses Casandra , Gasca-Velázquez Catalina , Luna-Barroso Cecilia , Marín-Pérez César , Calderon-Camacho Cinthia , Hernandez-Perez Cinthia , Hernández-Peralta Cinthia Xóchitl , Castillo-Rioja Clarinet , Bustamante-Durán Claudia , Espinosa-Quintana Claudia Elizabeth , Galicia-Flores Claudia Lilia , Villagomez-Piña Claudia Lizbeth , Sierra-Martinez Cynthya Berenice , Fernández-Corona Daniel , Ordaz-Jiménez Daniel , Hernandez-Castillo Daniela Oreli , Ramirez-Aranda Daniela , Lopez-Guzman Dante Zazhil , del Monte-Homobono Diana , Gonzalez-Enciso Diana Isabel , Bolanos-Hernandez Diana Laura , Valdez-Solano Edith Elizabeth , Gonzalez-Torres Edith , Mercado-Hernández Edson Alfonso , Alvarado-Valle Eduardo , Morales-Martinez Elisa , Gonzalez Elizabet , Díaz-Martínez Elsa Yadira , Vázquez-Torres Elvia Isabel , Ramos-Mendoza Elvira , del Rio-Gonzalez Emiliano , Alpizar-Flores Erika , García-García Erika , Pérez-Romero Erika , Sanchez-Martinez Esmeralda , Perez-Perez Estefania , López-García Estela Beatriz , Moran-De Los Santos Estela Elisabeth , Jerónimo-Hernández Esther , Estefes-Hernández Eva María , Sanchez-Alvarez Evelin , de Jesus Ramirez-Tinajero Felipe , Rivera-Cortés Felipe , Lopez-Tellez Francisca Ana Yetzy , Barajas-Soto Francisco , Garcia-Gonzalez Francisco Javier , Ruvalcaba-López Francisco Javier , Jimenez-Vasquez Gabriel Enrique , López-Villaseca Gabriela , Paredes-Cruz Gabriela , Rivera-Arredondo Gabriela , Nieto-Valenciano Gardenia , Balderas-Martinez Genaro , Limon Genoveva , Álvarez-Mancilla Gerardo , Gómez-Dorantes Gerardo Fernando , Villegas-Ramirez Gladis , Cruz-Angeles Gloria , Hernández-Buendía Gloria , Jimenez-Perez Grecia , Juárez-Salazar Guadalupe América , Garduño-Loyola Guadalupe , Villaseñor-Flores Hector Hugo , Velasco Hector M. , Villanueva-Cervantes Hector Valentin , Mendiola Hectorchavez , Rodríguez-Neria Hilda Nelly , Lobato-Garcia Hipatia , Torres-Morales Hortencia , Hernández-Peralta Idith Fabiola , Ochoa-Ramos Ingrid Alejandra , Morales-Casillas Irais , Abuhatab Irene , Garduño-Medina Irma , Palacios-Rivas Irma , Hernandez-Machuca Irving , Ramirez-Ramirez Irving Israel , Dominguez-Ursula Isabel , Prado-Morales Isamar , Barrios-Custodia Israel Adrian , Abrajan-García Ivan , Aguilar-Flores Ivonne Jazmín , Rodriguez-Castro Jaime Alfonso , Alvarado-Lopez Jaime Lee , Guadarrama-Fernández Jaqueline , Lopez-Lopez Jaqueline , Pablo-Bautista Jaredhia Nathaly , Martinez-Ramirez Jedini Paola , Mendoza-Mendoza Jennifer , Vázquez-Bustamamnte Jessica Elena , Ramírez-Gonzalez Joaquín Edmundo , Hernández-Arellano Jorge , Ocana-Monroy Jorge L. , Medina-Torres Jorge Ricardo , Zavala-Barrera Jose Alberto , Lemus-Enciso Jose Cristian Alexis , Barajas-Gónzalez José Juan , Castañeda-Dorantes José Juan , Ocana-Monroy Jose Luis , Alvarado-Calderón Josefina , Sanchez-Escudero Josefina , Garcia-Pantoja Joselyn Adali , Hernandez-Salinas Juan Adan , Cruz-Hernandez Juan Carlos , Medina-Hernández Juan Carlos , Rodríguez-Ramírez Juan Carlos , Pérez-Álvarez Juan Gabriel , Hernandez-Canales Juan Pablo , Marines-Álvarez Juan Rubén , Romero-Becerril Juana Patricia , Gómez-Dorantes Julio César , Ortiz-Sanchez Julio , Ramos-Perez Karina Adriana , Ayala-Escamilla Karina , Sánchez-Ramírez Karina , Zárate-Barrios Karla Patricia , Arroyo-Garfias Laura , Cordoba-Barrios Laura , Limon-Espinoza Laura , Magallón-Nava Laura , Rodriguez-Camacho Lesley Geraldine , Avendano-Baltierra Leslie Andrea , Rubio-Rojas Leslie Nancy , Cruz-Castañeda Leticia , Martínez-Morales Leticia , Arias-Lezama Lezly Fernanda , Reséndiz-Galván Lilia , Rodríguez-Ayala Liliana , Solano-Vazquez Liliana , Velazco-Valdez Lina , Armendáriz-Zahuantitla Lizbeth , Castro Lizbeth , Torres-Vázquez Lucía , Loa-Orellana Luis Antonio , Vazquez-Padilla Luis Arturo , Toriz-Nava Luis Brandon , Salcedo-Sandoval Luis Ivan , Valdez-Rivera Luis Manuel , Morales-Torres Luz Xochiquetzalit , Camacho-Estrella Maciel Areli , Tapia-Gómez Macrina , Caballero-Sanchez Magali Abigail , Martínez-López Magaly Lizbeth , Sánchez-Salinas Magdalena , Gonzalez-Carranza Marco Antonio , Montes-Mérida Marco Antonio , Salazar-Giron Marco Antonio , Torres-Rodríguez Margarita Mirta , Meléndez-Hernández María Alejandra , Ramos-Mendoza María Alejandra , Dominguez-Romero Maria Alexandra , Antonia-González María , Pérez-Vargas María Aurora , Rojas-Aguilar María Beatriz , Ruiz-Flores María Cristina , de los A ngeles Chavez-Corona Maria , del Carmen Montiel-Pérez María , del Carmen Novelo-Aguilar María , Espinoza-Pérez María Elena , González-Ruiz María Elena , Maya-Colin María Estela , Kennedy-Vazquez Maria Fernanda , Hernandez-Soler Maria , Medina-Torales María Isabel , Olvera-González María , Hernandez-Melendez Maria Priscila , Villa-Botello María Teresa , Labastida-Luna Mariana Andrea , Bolanos-Orduna Mariana , Rodríguez-Ledezma Maribel , Gomez-Collado Marisol , López-Arredondo Marisol , Villa-Ayala Marissa , Alvarez-Marin Martha , Decimo-Canales Martha , Flores-Hernández Martha , Flores-Ortiz Martin , Linas-Sanchez Martin , Marin-Sanchez Mauricio , Salado-Bazán Mayeli , Chagolla-Reyes Mayra , Marquez-Jimenez Mayranni , Martinez-Medina Miguel Angel , Salgado-Martinez Miguel , Olivos-Rivera Misael , Sánchez-Cejudo Moisés , Gónzalez-Ramos Mónica Ernestina , Gomez-Abad Monica , Irineo-Ugarte Mónica , Martínez Mónica , Martínez-Márquez Mónica , Castillo-Ramos Nancy Abigail , Hernández-Galicia Nancy Patricia , Elizarraras-Torres Natalia Guadalupe , Tinoco-Hernandez Natalia , Reyna-Salgado Neri , Velázquez-Mandujano Noé , Zurita-Morán Noemí , Esteban-Cruz Norma Alicia , Orbe-Sierra Norma Angelica , Solís-Calvillo Norma Patricia , Rivera-Cortez Oliverio , Santiago-Perez Omar , Hernandez-Camacho Oswaldo , Gómez-Dorantes Oswaldo Israel , Andrés-Gutiérrez Patricia , Cuarenta-Medina Patricia , Rez Patricia , Marquez-Espino Patricio , Morales-Godinez Paula , Montano-Rojas Paulina Monserrat , Bravo-Juarez Ramses Alejandro , Garza-Zepeda Reyna Aurora , Contreras-Hernández Reyna Margarita , Ruiz-Zepeda Ricardo Manuel , Marquez-Nunez Ricardo , Pelaez-Granados Roberto Fabian , Solera-Calvo Roberto , Hernández-López Rocío , García-Anaya Rosalinda , Lujan-Velazquez Rosario Dafne , Rul-Rivero Rosario Pérez , Vazquez-Reyes Rosaura , Espinoza-Peña Rubén , García-Pérez Ruperto , González-Garrido Salomón , Nayeli-De la Rosa Rodríguez Samantha , Colon-Serrano Sandra Lizbet , García-Hernández Sanjuana , Olvera-Arriaga Santiago , Pérez-Gallardo Santos , Heras-Santiago Sara , Flores-Jimenez Sara Yazmin , Montiel-Sanchez Sarahi , Bruno-Baltazar Sérgio César , Cruz-Martinez Sheila , Luna-Ramírez Sibyl Nadir , Ávila-Jaen Silvia , Cervantes-Saldívar Silvia , Cardenas-Valencia Socrates , Saldívar-Sánchez Sonia Angélica , Sanchez-Damiz Tania Michelle , Dorantes-Rosas Tomás , Lopez-Sanchez Vera , Colín-Hernández Verónica , Perez-Elizalde Veronica , Sanchez-Ortega Veronica , Santos-Sánchez Verónica , Velasco-Nava Veronica , Hernandez-Piña Vianey , Flores-Ramírez Violeta , Ruiz-Gonzalez Viridiana , Mejia-Villegas Xiadani Paulina , Cano-Goméz Xóchitl , Mondragón-Martínez Yacquelín , Evaristo-Montes Yamili , Carcia-Muñoz Yaquelinne , Mendoza-Rocafuerte Yaxum , Parra-Ortega Yazmin , Guadarrama-Fernández Yeni Guadalupe , Martinez-Morales Yojahira , Martinez-Vite Zaira Rebeca , Lucio-Olmedo Zoraida ,   Data management, programming and statistics, Rivas-Reyes Fernando , Ramírez-Reyes Raúl ,   Epidemiology, Garcilazo-Ávila Adrián , Gonzáles-Carballo Carlos , Aguilar-Ramírez Diego , Zhu Doreen , Trichia Eirini , Chiquete Erwin , Bragg Fiona , Whitlock Gary , Friedrichs Louisa Gnatiuc , Staplin Natalie , Bello-Chavolla Omar Yaxmehen , Haynes Richard , Clarke Robert , Lewington Sarah , Herrington William ,   Field transportation,   Genetics and bioinformatics, Vergara Alejandra , Barrera-Sánchez Elizabeth , Del Vecchyo-Tenorio Georgina , González-Ruiz Margarita , Baca-Peynado Paulina , Liu Tianshu , Wang Yunhe ,   Laboratory operations, Wong Adriana Lucrecia Wong y. , Magos Clementina , Romer Fredrik , Martínez Herendira Zambrano , Wheeler James , Emmens Kathleen , Youngman Linda , Radley Martin , Sanchez Martha Solano , Lacey Matthew , Hill Michael R. , Plunkett Nigel , Taylor Paul , Shellard Richard , Clark Sarah , Williams Tim ,   Project management, Fernandez Gustavo Olaiz , Holland Lisa , Cervantes Malaquias López , Baras Aris , Hill Michael R. , Emberson Jonathan R. , Marchini Jonathan , Kuri-Morales Pablo , Tapia-Conyer Roberto 
Published: October 2023

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.