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, Del Pilar Lopez Andrea, 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, Talkowski Michael E, Daly Mark J, Mahjani Behrang, De Rubeis Silvia, Cook Edwin H, Roeder Kathryn, Betancur Catalina, Devlin Bernie, Buxbaum Joseph D
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
medRxiv. 2025 Jan 6:2024.12.27.24319460. doi: 10.1101/2024.12.27.24319460.
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., , , , ) 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.
在过去十年中，在识别那些受有害编码变异影响时会导致自闭症谱系障碍（ASD）、智力残疾和其他发育障碍高风险的基因方面取得了显著进展。然而，大多数潜在基因发现工作都集中在欧洲血统的个体上，限制了对不同人群遗传风险的深入了解。为了帮助解决这一问题，拉丁美洲血统自闭症基因组学联盟（GALA）成立，在此展示了拉丁美洲个体中规模最大的ASD测序研究（n>15,000）。我们鉴定出35个全基因组显著（FDR<0.05）的ASD风险基因，与欧洲队列的研究结果有大量重叠，并且高度受限的基因在不同人群中显示出一致的信号。这些结果为新出现的（例如， ， ， ）和已确定的ASD基因提供了支持，也为不同人群中有害变异的基因检测方法的实用性提供了支持，同时也表明持续需要更具包容性的基因研究和检测。我们得出结论，ASD的生物学机制是普遍的，不受血统的任何可检测程度的影响。
