Discovery of Eight New Genes Linked to Schizophrenia Enhances Understanding of the Disorder

Scientists have identified eight new genes associated with schizophrenia through the largest exome-sequencing study conducted to date. The researchers, affiliated with the Centre for Neuropsychiatric Genetics and Genomics (CNGG) at Cardiff University, analyzed genetic data from nearly 29,000 individuals diagnosed with schizophrenia, over 103,000 without the condition, and more than 3,400 families affected by the disorder. Their findings, published in Nature Communications, provide critical insights into the genetic underpinnings of schizophrenia and open new avenues for developing targeted treatments.

The study focused on detecting rare, high-impact mutations in protein-coding genes that appear more frequently in individuals with schizophrenia. Among the eight genes identified, two—STAG1 and ZNF136—showed strong genetic associations with the disorder. The remaining six genes—SLC6A1, KLC1, PCLO, ZMYND11, BSCL2, and CGREF—demonstrated more moderate evidence of involvement.

Significantly, SLC6A1 and KLC1 are the first genes linked to schizophrenia exclusively through missense variants, which are mutations that result in changes to amino acids in proteins. This discovery underscores the importance of specific mutation types in understanding the genetic risk factors for schizophrenia.

According to Dr. Sophie Chick, a Ph.D. student at Cardiff University, these findings suggest that abnormalities in DNA organization within cells and disruptions in GABA-mediated communication among brain cells are involved in the disorder. This research advances our comprehension of the neurobiological complexity of schizophrenia and fosters hope for future drug development.

The study also highlights genetic overlaps between schizophrenia and other neurodevelopmental conditions such as autism, epilepsy, and developmental delays. Notably, four of the newly identified genes—STAG1, SLC6A1, ZMYND11, and CGREF1—have prior links to these disorders.

Dr. Elliott Rees, the lead author, noted that while rare genetic variants have been implicated in schizophrenia, pinpointing specific genes has been challenging. These new discoveries significantly broaden the catalog of genes associated with the disorder, providing a genetic blueprint for future research into its underlying mechanisms.

While translating these genetic insights into therapeutic interventions remains a long-term goal, the findings mark a substantial step forward in understanding the intricate genetics of schizophrenia and could guide the development of more effective, personalized treatments.