Global Collaboration Finds Genes that May Increase Risk of Schizophrenia

What’s New in Psychology?

Global Collaboration Finds Genes that May Increase Risk of Schizophrenia  

Jim Windell

                  What are the root causes of Schizophrenia?

                 Are those causes purely psychological or are they biological?

            The causes of schizophrenia are important to determine because schizophrenia is a serious mental disorder in which people interpret reality abnormally and often experience hallucinations, delusions, and extremely disordered thinking and behavior that usually has an impact on daily functioning. People with schizophrenia are typically diagnosed between the ages of 16 and 30, and statistics suggest that schizophrenia may affect as many as 2.8 million people in the U.S.

            To that end of learning more about the cause of schizophrenia, a landmark genetic study of more than 121,000 people has identified extremely rare protein-disrupting mutations in 10 genes that strongly increase an individual's risk of developing schizophrenia. The study was carried out by an international consortium called SCHizophrenia Exome Meta-Analysis (SCHEMA), led by researchers at the Broad Institute of MIT and Harvard. Additionally, The Genomic Psychiatry Cohort (GPC) study, based at Rutgers, The State University of New Jersey and led by Drs. Carlos and Michele Pato, were major contributors to this study as well as a second, complementary study, led by researchers at Cardiff University on behalf of the Psychiatric Genomics Consortium (PGC). The PGC study is based on a larger but overlapping group of 320,400 people and brings to 287 the number of regions of the genome associated with schizophrenia risk, including ones containing genes identified by SCHEMA.

           Taken 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. Two studies appeared together recently in the journal Nature. Another related study was published in Nature Genetics.

           According to Benjamin Neale, a co-corresponding author on the SCHEMA study and a PGC collaborator, who is on the faculty of the Department of Medicine's Analytic & Translational Genetics Unit (ATGU) at Massachusetts General Hospital, “Identifying these 10 genes is a watershed moment in schizophrenia research because each one of them provides a solid foundation for launching biological inquiry. Neale added that “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.”

           And Stanley Center for Psychiatric Research director at Broad University, Steven Hyman, said: “We've tried for years and years to gain this kind of traction on the biology of schizophrenia. Realistically, it will take yet more years to translate these results into biomarkers and treatments that will make a difference in the lives of people who are suffering with this devastating illness. But it is highly motivating to have a compelling path forward.”

           Furthermore, as Carlos Pato, executive chair of psychiatry at Rutgers Biomedical and Health Sciences (RBHS) and co-lead of the GPC study based at Rutgers, explained, “The advances being made in these studies begin to clarify converging biology and physiology that can be targets for new treatment development.”

           The ultra-rare variants in 10 genes that have been identified and that dramatically increase a person's risk of developing schizophrenia are called PTVs. PTVs, or “protein truncating variants,” prevent cells from producing a gene’s full-length functional protein. The findings, reported on in Nature, also hint at an additional 22 genes that may likely influence schizophrenia risk, and which may prove significant after further study.

           “These first 10 genes are really only the beginning of genetic discovery,” Neale said. “There is pretty clear evidence that there are many more genes to discover using the same kind of approach. But we fundamentally need bigger sample sizes to be able to reveal those additional genes.”

           To read the original articles, find them with these references:

Singh TJ, Neale BM, Daly MJ, and the Schizophrenia Exome Meta-Analysis (SCHEMA) Consortium. Rare coding variants in 10 genes confer substantial risk for schizophrenia. Nature. Online April 6, 2022. DOI: 10.1038/s41586-022-04556-w

The Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ripke S, Walters JTR, and O’Donovan MC. Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia. Nature. Online April 6, 2022. DOI: 10.1038/s41586-022-04434-5

Palmer DS, and the Bipolar Exome Consortium. Exome sequencing in bipolar disorder reveals shared risk gene AKAP11 with schizophrenia. Nature Genetics. Online April 6, 2022. DOI: 10.1038/s41588-022-01034-x


Share this post:

Comments on "Global Collaboration Finds Genes that May Increase Risk of Schizophrenia "

Comments 0-5 of 0

Please login to comment