A study led by Professor Yoo Hee-jeong of psychiatry at Seoul National University Bundang Hospital (SNUBH) has taken a crucial step in understanding the genetic roots of autism in Korea.

For the first time, researchers have analyzed the East Asia's largest dataset of Korean family genomes to uncover the genetic factors driving autism and its varying manifestations between genders, the hospital said.

Autism spectrum disorder, which affects social interaction and is marked by restricted and repetitive behaviors, remains a puzzle in medical science. Although it’s known to occur about four times more frequently in males, the genetic reasons behind this disparity are not fully understood. Adding to the challenge, most existing research has centered on North American and European populations, leaving a knowledge gap in East Asia.

To bridge this divide, Professor Yoo’s team collaborated with Professor An Joon-yong from Korea University’s School of Biosystem and Biomedical Science, Professor Kim Eun-joon from the Institute for Basic Science’s Synaptic Brain Dysfunctions, and Professor Donna Werling from the University of Wisconsin-Madison’s Laboratory of Genetics.

Together, the team analyzed genomic data from 673 Korean families—consisting of 2,255 individuals—who have autistic members, revealing gender-specific autism risk genes that were previously unknown.

The findings, published in Genome Medicine (IF 15.26) in September, revealed distinct gender-specific genetic pathways linked to autism: in males, autism-related genes primarily impact synapses—the structures that enable neuron-to-neuron communication—while in females, these genes affect chromatin and histones, essential in regulating gene expression. “This suggests that autism may arise through fundamentally different mechanisms between genders,” an SNUBH spokesperson said. 

Moreover, the study found that autistic females carry a higher number of protein-truncating variants, which hinder protein function, compared to autistic males. Among families with autism, females also exhibited higher quantitative genetic scores for autism than males. 

Yet, consistent with prior research from North America and Europe, females displayed a lower prevalence and severity of autism, indicating a potentially greater resilience to the genetic factors associated with the disorder.

Professor An said this study is significant as it has established a foundation for sex-based medicine in Koreans, based on whole-genome data. “It is particularly meaningful because it identified genetic causes by focusing on Korean autism patients and their families, instead of North American and European populations,” he said. 

“As the first large-scale genomic study on autism in Koreans, the research holds promise for advancing early detection and gender-responsive, personalized autism treatments in East Asia,” the SNUBH said.