People with autism spectrum disorder (ASD) and schizophrenia from different populations around the world may share common genetic variants, according to a new Japanese study published in the journal Cell Reports.

Supporting previous work conducted with Caucasians, the researchers found that Japanese individuals with autism spectrum disorder and schizophrenia also have overlapping copy number variations. A copy number variation (CNV) is when the number of copies of a particular gene varies from one person to the next.

“Genetic overlap has been suggested in epidemiological and molecular genetic studies,” said first author Itaru Kushima of Nagoya University Graduate School of Medicine in Japan. “In line with this, our systematic and comprehensive investigation confirmed a significant overlap of pathogenic CNVs between autism spectrum disorder and schizophrenia in a Japanese population.”

ASD and schizophrenia have complex inheritance patterns with multiple genetic and environmental factors influencing the risk for both conditions. And while the two disorders are clinically distinct, research points to a genetic overlap between them.

For example, the disorders tend to co-occur at a higher rate than would be expected in the general population, and a large epidemiological study showed that a family history of schizophrenia in first-degree relatives is a risk factor for autism spectrum disorder.

In particular, previous research has shown that the two disorders are associated with an increased burden of CNVs, and rare CNVs in specific locations are shared risk factors for both disorders.

However, most research has been conducted with Caucasian populations, limiting the generalization of pathogenic CNVs and relevant biological pathways. Therefore, studies with non-Caucasian populations would provide important biological insights.

To address this gap in knowledge, senior study author Dr. Norio Ozaki at Nagoya University Graduate School of Medicine and his team performed comparative CNV analyses of 1,108 individuals with ASD, 2,458 with schizophrenia, and 2,095 controls in a Japanese population. They used a high-resolution technique called array comparative genomic hybridization.

Their findings confirmed an increased genome-wide burden of rare CNVs in ASD and schizophrenia and observed an overlap in pathogenic CNVs between the two disorders.

Pathogenic CNVs including those at 29 locations common to both disorders were found in about 8 percent of the two types of patients, which was significantly higher than in controls.

“The strength of our study is the systematic head-to-head comparison of pathogenic CNVs and biological pathways between autism spectrum disorder and schizophrenia,” Ozaki said. “Previous studies in Caucasian populations found overlap in pathogenic CNVs between the two disorders, but their analyses were limited to a small number of genes and CNV loci.”

Additional analysis revealed that both disorders are associated with overlapping biological pathways involved in the oxidative stress response, lipid metabolism, and genomic integrity. The researchers also identified 12 CNV locations potentially associated with these disorders in a Japanese population.

Furthermore, intellectual disability was strongly associated with pathogenic CNVs in both patient groups. “The identification of shared pathways and disease-relevant genes provides biological insights into autism spectrum disorder and schizophrenia,” Ozaki said.

Source: Cell Press