Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders

Researchers just found common genes linked to autism, ADHD, schizophrenia, bipolar disorder, major depressive disorder, Tourette syndrome, obsessive-compulsive disorder, and anorexia.

These disorders all share common genetic variants that influence brain development.

Researchers found that these genetic differences impact multiple stages of brain growth and are involved in complex protein interactions. This discovery could explain why many of these conditions often appear together in individuals and families, offering a fresh perspective on mental health connections.

By identifying 683 genetic variants that regulate brain development, scientists hope to pave the way for new treatments targeting these shared genetic factors. This research challenges traditional classifications of psychiatric disorders and suggests that a single therapy could potentially address multiple conditions. With nearly 1 billion people worldwide affected by mental health disorders, these findings mark a significant step toward more effective, genetically-informed treatments.

This is the abstract to the article, and the full reference can be found below:

A meta-genome-wide association study across eight psychiatric disorders has highlighted the genetic architecture of pleiotropy in major psychiatric disorders. However, mechanisms underlying pleiotropic effects of the associated variants remain to be explored. We conducted a massively parallel reporter assay to decode the regulatory logic of variants with pleiotropic and disorder-specific effects. Pleiotropic variants differ from disorder-specific variants by exhibiting chromatin accessibility that extends across diverse cell types in the neuronal lineage and by altering motifs for transcription factors with higher connectivity in protein-protein interaction networks. We mapped pleiotropic and disorder-specific variants to putative target genes using functional genomics approaches and CRISPR perturbation. In vivo CRISPR perturbation of a pleiotropic and a disorder-specific gene suggests that pleiotropy may involve the regulation of genes expressed broadly across neuronal cell types and with higher network connectivity.

https://www.cell.com/cell/abstract/S0092-8674(24)01435-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867424014351%3Fshowall%3Dtrue&fbclid=IwY2xjawI0q1BleHRuA2FlbQIxMAABHZIsTNmGDZ-OaIPrFilQARje_GTDpqEZJ24rLKsL-daqHb2sILag-Wo6zw_aem_C8UZfHF-bWAva4Y7NnOgpw