Deleterious coding variation associated with autism is consistent across populations, as exemplified by admixed Latin American populations
Authors: Avila Marina Natividad , Jung Seulgi , Satterstrom F. Kyle , Fu Jack M. , Levy Tess , Sloofman Laura G. , Klei Lambertus , Pichardo Thariana , Stevens Christine R. , Cusick Caroline M. , Ames Jennifer L. , Campos Gabriele S. , Cerros Hilda , Chaskel Roberto , Costa Claudia I. S. , Cuccaro Michael L. , Lopez Andrea del Pilar , Fernandez Magdalena , Ferro Eugenio , Galeano Liliana , Girardi Ana Cristina D. E. S. , Griswold Anthony J. , Hernandez Luis C. , Lourenço Naila , Ludena Yunin , Nuñez Diana L. , Oyama Rosa , Peña Katherine P. , Pessah Isaac , Schmidt Rebecca , Sweeney Holly M. , Tolentino Lizbeth , Wang Jaqueline Y. T. , Albores-Gallo Lilia , Croen Lisa A. , Cruz-Fuentes Carlos S. , Hertz-Picciotto Irva , Kolevzon Alexander , Lattig Maria C. , Mayo Liliana , Passos-Bueno Maria Rita , Pericak-Vance Margaret A. , Siper Paige M. , Tassone Flora , Trelles M. Pilar ,   Autism Sequencing Consortium, Talkowski Michael E. , Daly Mark J. , Mahjani Behrang , De Rubeis Silvia , Cook Edwin H. , Roeder Kathryn , Betancur Catalina , Devlin Bernie , Buxbaum Joseph D. 
Published: January 2025

The past decade has seen remarkable progress in identifying genes that, when impacted by deleterious coding variation, confer high risk for autism spectrum disorder (ASD), intellectual disability, and other developmental disorders. However, most underlying gene discovery efforts have focused on individuals of European ancestry, limiting insights into genetic risks across diverse populations. To help address this, the Genomics of Autism in Latin American Ancestries Consortium (GALA) was formed, presenting here the largest sequencing study of ASD in Latin American individuals (n>15,000). We identified 35 genome-wide significant (FDR < 0.05) ASD risk genes, with substantial overlap with findings from European cohorts, and highly constrained genes showing consistent signal across populations. The results provide support for emerging (e.g.,MARK2,YWHAG,PACS1,RERE, SPEN, GSE1, GLS, TNPO3, ANKRD17) and established ASD genes, and for the utility of genetic testing approaches for deleterious variants in diverse populations, while also demonstrating the ongoing need for more inclusive genetic research and testing. We conclude that the biology of ASD is universal and not impacted to any detectable degree by ancestry.

Autism Sequencing Consortium (ASC)

Branko Aleksic, Mykyta Artomov, Mafalda Barbosa, Elisa Benetti, Catalina Betancur, Monica Biscaldi-Schafer, Anders D. Børglum, Harrison Brand, Alfredo Brusco, Joseph D. Buxbaum, Gabriele Campos, Simona Cardaropoli, Diana Carli, Angel Carracedo, Marcus C. Y. Chan, Andreas G. Chiocchetti, Brian H. Y. Chung, Brett Collins, Ryan L. Collins, Edwin H. Cook, Hilary Coon, Claudia I. S. Costa, Michael L. Cuccaro, David J. Cutler, Mark J. Daly, Silvia De Rubeis, Bernie Devlin, Ryan N. Doan, Enrico Domenici, Shan Dong, Chiara Fallerini, Magdalena Fernandez, Montserrat Fernández-Prieto, Giovanni Battista Ferrero, Eugenio Ferro, Jennifer Foss Feig, Christine M. Freitag, Jack M. Fu, Liliana Galeano, J. Jay Gargus, Sherif Gerges, Elisa Giorgio, Ana Cristina Girardi, Stephen Guter, Emily Hansen-Kiss, Erina Hara, Danielle Halpern, Gail E. Herman, Luis C. Hernandez, Irva Hertz-Picciotto, David M. Hougaard, Christina M. Hultman, Suma Jacob, Miia Kaartinen, Lambertus Klei, Alexander Kolevzon, Itaru Kushima, Maria C. Lattig, So Lun Lee, Terho Lehtimäki, Lindsay Liang, Carla Lintas, Alicia Ljungdahl, Andrea del Pilar Lopez, Caterina Lo Rizzo, Yunin Ludena, Patricia Maciel, Behrang Mahjani, Nell Maltman, Marianna Manara, Dara S. Manoach, Dalia Marquez, Gal Meiri, Idan Menashe, Judith Miller, Nancy Minshew, Matthew Mosconi, Marina Natividad Avila, Rachel Nguyen, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Lisa Pavinato, Katherine P. Peña, Minshi Peng, Margaret Pericak-Vance, Antonio M. Persico, Isaac N. Pessah, Thariana Pichardo, Kaija Puura, Abraham Reichenberg, Alessandra Renieri, Kathryn Roeder, Catherine Sancimino, Stephan J. Sanders, Sven Sandin, F. Kyle Satterstrom, Stephen W. Scherer, Sabine Schlitt, Rebecca J. Schmidt, Lauren Schmitt, Katja Schneider-Momm, Paige M. Siper, Laura Sloofman, Moyra Smith, Renee Soufer, Christine R. Stevens, Pål Suren, James S. Sutcliffe, John A. Sweeney, Michael E. Talkowski, Flora Tassone, Karoline Teufel, Elisabetta Trabetti, Slavica Trajkova, Maria del Pilar Trelles, Brie Wamsley, Jaqueline Y. T. Wang, Lauren A. Weiss, Mullin H. C. Yu, Ryan Yuen, Jessica Zweifach.