Landmark study reveals clearest genetic signals yet for schizophrenia risk
This and another large genetic study point to similar genes and biological mechanisms that start to home in on the root causes of the severe psychiatric disorder
April 6, 2022
In a landmark genetic study of more than 121,000 people, an international consortium called SCHEMA, led by researchers at the Broad Institute of MIT and Harvard, has identified extremely rare protein-disrupting mutations in 10 genes that strongly increase an individual’s risk of developing schizophrenia — in one instance, by more than 20-fold. A second, complementary study in a larger but overlapping group of 320,400 people, conducted by the Psychiatric Genomics Consortium (PGC) and including the same Broad researchers, brings to 287 the number of regions of the genome associated with schizophrenia risk, including ones containing genes identified by SCHEMA.
Together, these studies underscore an emerging view of schizophrenia as a breakdown in communication at the synapse (the junction between neurons), and illustrate how different kinds of genetic variation affecting the same genes can influence the risk for different psychiatric and neurodevelopmental disorders. The two studies appear together in the journal Nature.
“Psychiatric disorders have been a black box for a very long time. Unlike cardiovascular disease or cancer, we have had very few biological clues to disease mechanisms,” said Tarjinder Singh, a postdoctoral fellow in the Stanley Center for Psychiatric Research at the Broad Institute. “As a result, we have lacked the necessary insights for development of much needed new treatments. Instead we have been iterating on the antipsychotic drugs serendipitously discovered more than 70 years ago.” Singh, who is also in the Analytic and Translational Genetics Unit (ATGU) at Massachusetts General Hospital, is a collaborator on the PGC study, and a co-corresponding author of the SCHEMA study.
“Identifying these 10 genes is a watershed moment in schizophrenia research because each one of them provides a solid foundation for launching biological inquiry,” said Benjamin Neale, another co-corresponding author on the SCHEMA study, a PGC collaborator, an institute member and director of genetics in the Stanley Center, co-director of the institute’s Program in Medical and Population Genetics, and faculty of the Mass General ATGU. “By sequencing the DNA of thousands of people, we are starting to see exactly which genes matter. These discoveries are the starting point for developing new therapies that treat the root cause of this devastating condition.”