FUNDED PROJECTS

Schizophrenia is a common severely disabling disease, associated with ≈15-year reduction in life span. Schizophrenia is strongly influenced by genetic factors; however, the genetic basis of schizophrenia is far from being understood.

Common genetic variants discovered so far are associated with only tiny changes in disease risk and they typically have no known or even speculated mechanism. Studies searching for rare variants with clear biological function have had a few successes; however, further progress requires extremely large sample sizes. Thus, current research findings on the genetics of schizophrenia are difficult to translate to potential treatments.
To discover new schizophrenia risk genes, our project takes a novel approach to recruitment and characterization of patients.

Our approach has the following key components:

(1) Recruitment of schizophrenia patients with severe symptoms.

(2) Recruitment of Ashkenazi Jewish patients, given the very small historical size of the population, which may have led to some risk variants being present at relatively high frequencies.

(3) Recruitment of additional patients from other currently or formerly isolated minority Israeli populations (such as Yemenite Jews, Druze, and Bedouin).

(4) Integration of the data from our patients into Psifas, Israel’s national precision medicine initiative, which will provide us access to up to 100k controls.

(5) Automatic extraction of comprehensive longitudinal electronic medical records of our patients.

(6) Deep sequencing of the entire genomes of all patients, which will allow us to investigate all types of genetic variation.

The project will create a highly valuable resource for genomic studies in mental health, will increase the diversity of genomic studies, and will generate new insights on the genetic basis on schizophrenia and its symptoms.