Research reveals hidden genetic mechanisms behind psychiatric disorders

In a comprehensive review of recent genetic studies, researchers have identified a hidden layer of complexity in how our genes function, shedding new light on the biological underpinnings of major psychiatric disorders. The study published in Genomic psychiatry reveals that a process called alternative polyadenylation (APA) – which affects the way genes are expressed – may be a crucial factor in determining a person’s risk for conditions such as schizophrenia, bipolar disorder and depression. This discovery opens up exciting new avenues for understanding and potentially treating these complex mental health conditions.

“We’ve known for years that psychiatric disorders have a strong genetic component, but it’s been challenging to pinpoint exactly how genes contribute to disease risk,” said Dr. Michelle Paff, lead author of the study. “Our research shows that it’s not just which genes you have, but how those genes are processed and regulated.”

The study focuses on APA, a mechanism that affects the stability and localization of messenger RNA (mRNA) molecules, which serve as blueprints for protein production in cells. By changing the length of a gene’s 3′ untranslated region (3’UTR), APA can have a significant impact on how much protein is produced by a particular gene and where in the cell that protein ends up.

Using advanced computational techniques, the researchers analyzed data from multiple large-scale genetic studies, identifying 286 genes whose APA patterns were associated with psychiatric disorders. Remarkably, 60-65% of these genes had not previously been linked to these disorders via other genetic mechanisms.

“This finding suggests that APA may be a ‘missing link’ in our understanding of psychiatric genetics,” explained Dr. Xiangmin Xu, lead author of the study. “It helps explain why some individuals with genetic risk factors develop disorders while others do not.”

The research identified several specific genes in which APA appears to play a particularly important role:

• DDHD2: This gene is associated with the risk of schizophrenia. The APA pattern of this gene may affect the way neurons communicate.
• FADS1: Linked to bipolar disorder; changes in the APA of this gene may affect the metabolism of fatty acids that are crucial for brain function.
• GABRA2: Also associated with bipolar disorder. APA from this gene can disrupt the balance of inhibitory signaling in the brain.
• MTCH2: APA from this gene is linked to the risk of depression. It may affect mitochondrial function and energy production in brain cells.

The researchers also found that genes affected by APA in psychiatric disorders are often involved in intracellular transport and cellular localization pathways. This suggests that APA may affect how proteins are moved and positioned within neurons, potentially disrupting normal brain function.

“These findings have important implications for how we approach both the research and treatment of psychiatric disorders,” said Dr. Paff. “By understanding the role of APA, we may be able to develop more targeted therapies that address the root causes of these disorders at the molecular level.”

The study authors caution that more research is needed to fully understand the implications of these findings. However, they are optimistic about the potential of this work to lead to new diagnostic tools and treatment strategies.

“This line of work opens up a whole new dimension in psychiatric genetics,” Dr. Xu concluded. “It’s an exciting time in the field, and we believe this work will accelerate our progress toward better outcomes for individuals living with these challenging conditions.”

Provided by Genomic Press