Common Genes in Neuropsychiatric Disorders

Finding a specific genes linked to specific neuropsychiatric disorders has been a key research strategy.

However, this strategy has not been entirely successful.

One problem with this unitary approach is the diagnostic overlap and comorbidity common to neuropsychiatric disorders such as mood disorders and autism.

A promising alternative strategy is to focus on genes that share risk with more than one neuropsychiatric condition.

Amit Lotan from Israel along with colleagues from the Netherlands, Germany and the U.S. recently published a study of common and distinct genetic components in six major neuropsychiatric disorders.

Their study used large genome wide association databases mined from the National Human Genome Research Institute linked to the following six neuropsychiatric disorders:

• Anxiety disorders
• Attention deficit/hyperactivity disorder
• Autism/autism spectrum disorders
• Bipolar disorder
• Major depression 
• Schizophrenia

Using a variety of genetic and molecular biology strategies, the research team examined human and mouse genes common to more than one neuropsychiatric disorder as well as genes unique to only one of the six disorders.

The key findings of the study including identification of 15 genes common to five of the six disorders. 

The genes identified in this analysis shared known activity in neuronal function known as postsynaptic density. Additionally, these shared genes are known to influence immune as well as brain function.

Additionally, the research identified two genetic components shared by all six of the disorders. These two components were involved in neuronal projection, synaptic activity, CNS development and cellular process. In total, these two genetic components contributed to 20-30% of the genetic load.

Obviously, 20-30% is a significant shared genetic contribution but it leaves important genetic contributions specific to each of the six conditions. 

The authors conclude in their discussion:

".. it could be hypothesized that a common (pathologic) molecular infrastructure located to neural projections, cytoplasm (or possibly both) may be necessary to induce a primary vulnerability to develop a neuropsychiatric disorder. Further distinct molecular processes which build-up on top of this common infrastructure ultimately lead, in certain patients, to the development of one or another specific neuropsychiatric disorder."

This type of study provides significant insight into the complexity of genetic influences in neuropsychiatric disorders.

Examining shared genetic influences in different conditions can aid in understanding common pathophysiology mechanisms for distinct neuropsychiatric disorders. Additionally, these types of studies show the limitations of current diagnostic classification systems and may aid in future refinement of diagnostic systems.

Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below. 

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Lotan A, Fenckova M, Bralten J, Alttoa A, Dixson L, Williams RW, & van der Voet M (2014). Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders. Frontiers in neuroscience, 8 PMID: 25414627