60 new autism genes identified

AUG. 18, 2022--A new study led by Columbia researchers has uncovered 60 genes linked to autism spectrum disorder (ASD) that may provide important clues to the causes of autism across the full spectrum of the disorder.

“Overall, the genes we found may represent a different class of genes that are more directly associated with the core symptoms of ASD than previously discovered genes,” says Wendy Chung, MD, PhD, the Kennedy Family Professor of Pediatrics and chief of clinical genetics in the Department of Pediatrics at the Columbia University Vagelos College of Physicians and Surgeons.

The findings were published Aug. 18 in Nature Genetics.

Several genes have been previously linked to autism and as a group are responsible for about 20% of all cases. Most individuals who carry these genes have profound forms of autism and additional neurological issues, such as epilepsy and intellectual disability.

To uncover hidden autism genes that can explain the majority of cases, the researchers tapped into data from nearly 43,000 people with autism, including 35,000 individuals from the SPARK autism research study of the Simons Foundation.

Five of the genes identified by the new study have a more moderate impact on autism characteristics, including cognition, than previously discovered genes.

“We need to do more detailed studies including more individuals who carry these genes to understand how each gene contributes to the features of autism, but we think these genes will help us unravel the biological underpinnings that lead to most cases of autism,” Chung says.

The five newly identified genes also explain why autism often seems to run in families. Unlike previously known autism genes, which are due to de novo or new mutations, genetic variants in the five new genes were often inherited from the participant’s parents.

Chung says that many more moderate-effect genes remain to be discovered and finding them should help researchers better understand the biology of the brain and behavior across the full spectrum of autism.

More information

The paper, titled “Integrating de novo and inherited variants 1 in 42,607 autism cases identifies mutations in new moderate effect genes,” was published Aug. 18 in Nature Genetics.

All authors: Xueya Zhou (Columbia), Pamela Feliciano (Simons Foundation), Chang Shu (Columbia), Tianyun Wang (University of Washington School of Medicine and Peking University Health Science Center), Irina Astrovskaya (Simons Foundation), Jacob B. Hall (Simons Foundation), Joseph U. Obiajulu (Columbia), Jessica R. Wright (Simons Foundation), Shwetha C. Murali (University of Washington School of Medicine), Simon Xuming Xu (Simons Foundation), Leo Brueggeman (University of Iowa Carver College of Medicine), Taylor R. Thomas (University of Iowa Carver College of Medicine), Olena Marchenko (Simons Foundation), Christopher Fleisch (Simons Foundation), Sarah D. Barns (Simons Foundation), LeeAnne Green Snyder (Simons Foundation), Bing Han (Simons Foundation), Timothy S. Chang (David Geffen School of Medicine, University of California, Los Angeles), Tychele N. Turner (Washington University), William T. Harvey (University of Washington School of Medicine), Andrew Nishida (Oregon Health & Science University), Brian J. O’Roak (Oregon Health & Science University), Daniel H. Geschwind (David Geffen School of Medicine, University of California, Los Angeles), the SPARK Consortium, Jacob J. Michaelson (University of Iowa Carver College of Medicine), Natalia Volfovsky (Simons Foundation), Evan E. Eichler (University of Washington School of Medicine and Howard Hughes Medical Institute), Yufeng Shen (Columbia), and Wendy K. Chung (Columbia).

This research was supported in part by grants from the National Institutes of Health (R01MH101221, R01GM120609, 1K99MH117165, R01MH105527, and R01DC014489) and grants from the Simons Foundation (608045, 810018EE, 606450, 644038).

Wendy Chung serves on the Scientific Advisory Board of the Regeneron Genetics Center and is director of clinical research for the Simons Foundation Autism Research Initiative.