Deleterious coding variation associated with autism is shared across ancestries.
Natividad Avila M., Jung S., Satterstrom FK., Fu JM., Levy T., Sloofman LG., Klei L., Pichardo T., Marquez D., Stevens CR., Cusick CM., Ames JL., Campos GS., Cerros H., Chaskel R., Costa CIS., Cuccaro ML., Lopez ADP., Fernandez M., Ferro E., Galeano L., Girardi ACDES., Griswold AJ., Hernandez LC., Lourenço N., Ludena Y., Núñez-Ríos D., Oyama R., Peña KP., Pessah I., Schmidt R., Sweeney HM., Tolentino L., Wang JYT., Albores-Gallo L., Croen LA., Cruz-Fuentes CS., Hertz-Picciotto I., Kolevzon A., Lattig MC., Mayo L., Passos-Bueno MR., Pericak-Vance MA., Siper PM., Tassone F., Trelles MP., GALA Consortium ., Autism Sequencing Consortium (ASC) ., Talkowski ME., Daly MJ., Mahjani B., De Rubeis S., Cook EH., Roeder K., Betancur C., Devlin B., Buxbaum JD.
The past decade has seen remarkable progress in identifying genes that, when impacted by deleterious coding variation, confer high likelihood for autism spectrum disorder (ASD), intellectual disability and other associated developmental disorders. However, most underlying gene discovery efforts have focused on individuals of European ancestry, limiting insights into genetic liability across diverse populations. To help address this, the Genomics of Autism in Latin American Ancestries (GALA) Consortium was formed, presenting here the largest sequencing study of autism in Latin American individuals (n > 15,000, including 4,717 participants with an ASD diagnosis). We identified 35 genome-wide significant (false discovery rate < 0.05) autism-associated genes, with substantial overlap with findings from European cohorts, and highly constrained genes showing consistent signal across populations. The results provide support for emerging (for example, MARK2, YWHAG, PACS1, RERE, SPEN, GSE1, GLS, TNPO3 and ANKRD17) and established autism genes and for the utility of genetic testing approaches for deleterious variants in individuals from diverse backgrounds; the results also demonstrate the ongoing need for more inclusive genetic research and testing. We conclude that the biology of autism is consistent across populations, with no detectable influence of ancestry.