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Suspect Molecules Overlap in Autism, Schizophrenia, Bipolar Disorder

Shared patterns of gene expression may hold clues to disease processes

Science Update

Evidence has been mounting that some mental disorders share many of the same genetic risk factors. Now, researchers have discovered that this overlap extends to the molecular level – some of these suspect genes also turn on-and-off similarly in the brains of people with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder. These molecular signatures may hold clues to what goes wrong in the brain in these disorders—and potentially ways to better treat or even prevent them.

In search of such clues, Drs. Daniel Geschwind and Michael Gandal of the University of California Los Angeles (UCLA), and colleagues, examined gene expression in postmortem brains of people who had been diagnosed with autism spectrum disorder (ASD), schizophrenia, bipolar disorder, major depressive disorder, or alcoholism. One of the largest such efforts of its kind to date, the study, funded by the National Institute of Mental Health (NIMH), tapped brain molecular data resources gathered through the NIMH-funded PsychENCODE consortium, a data-sharing collaboration among NIMH grantees.

As reported February 9, 2018, in Science, the study demonstrated – for the first time – that disorders with a large overlap in genetic risk factors also had a large overlap in patterns of gene expression and shared dysfunction in similar molecular pathways. For example, the researchers found that synapse and neuro-immune functions were similarly impacted in autism, schizophrenia, and bipolar disorder.

“The results advance understanding of how risk factors across many genes contribute to the development of various mental disorders, in combination with environmental factors,” explained Geetha Senthil, Ph.D., of the NIMH Office of Genomics Research Coordination. “The study also highlights the importance of such large-scale team science efforts in gaining insights into the biology underlying mental disorders.”

Chart shows correlations of gene expression between mental disorders.

Overlap in molecular signatures across certain mental disorders is reflected in correlations of gene expression between mental disorders. For example, schizophrenia (SCZ) and bipolar disorder (BD) showed the most such gene expression overlap, followed by autism spectrum disorder (ASD) and schizophrenia (SCZ). Similar patterns of overlap have been found among risk genes for the disorders.

Source: Daniel Geschwind, M.D., Ph.D., UCLA.

Grants

MH106438, MH094714, MH103339, MH110927, MH100027,
 MH110920, MH103340, MH103365, MH103392, MH103340, MH103346, MH105472, MH094714, MH105898, MH102791, MH105881, MH103877, MH106934, RMH085542, MH093725, MH066392, MH080405, MH097276, MH-075916, M096891, MH084053S1, MH057881, MH057881S1, AG02219, AG05138, MH06692

For More Information

UCLA news release:
Autism, schizophrenia, bipolar disorder share molecular traits, study finds

Reference

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Gandal MJ, Haney JR, Parikshak NN, Leppa V, Ramaswami G, Hartl C, Schork AJ, Appadurai V, Buil A, Werge TM, Liu C, White KP; CommonMind Consortium; PsychENCODE Consortium; iPSYCH-BROAD Working Group, Horvath S, Geschwind DH. Science. 2018 Feb 9;359(6376):693-697. doi: 10.1126/science.aad6469. PMID:29439242