2,000 human brains yield clues to how genes raise risk for mental illnesses

It’s one thing to detect sites in the genome associated with mental disorders; it’s quite another to discover the biological mechanisms by which these changes in DNA work in the human brain to boost risk. In their first concerted effort to tackle the latter, 15 collaborating research teams of the National Institutes of Health-funded PsychENCODE Consortium(link is external) leveraged statistical power gained from a large sample of about 2000 postmortem human brains.

The teams published their findings in seven research articles, spotlighted on the cover of a “psychiatric genomics” special issue of Science — along with two in Translational Medicine and one in Science Advances — on Dec. 14, 2018. In addition, the consortium is sharing their data with the research community via the online PsychENCODE Knowledge Portal(link is external).

Applying newly uncovered secrets of the brain’s molecular architecture, they developed an artificial intelligence model that’s six times better than previous ones at predicting risk for mental disorders. They also pinpointed several hundred previously unknown risk genes for mental illnesses and linked many known risk variants to specific genes.

“For the first time, we now have a beginning of an understanding of the biology, the molecular pathophysiology, of schizophrenia, bipolar disorder and autism spectrum disorder (ASD),” said Thomas Lehner, Ph.D., M.P.H., director of the Office of Genomics Research Coordination (OGRC) of the National Institute of Mental Health (NIMH), which launched the PsychENCODE initiative in 2015.

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