Schizophrenia is a severe mental illness that afflicts approximately one percent of the world's population. Although it is clear that approximately a half of the liability to develop the disorder is genetic, few genes have been unequivocally implicated in the etiology of the disorder. Recent data from a large (~3,000 cases and 3,000 controls) study of copy number variations in schizophrenia found evidence for three rare deletions on chromosomes 1q, 15q and 22p that may cause schizophrenia. The evidence from these deletions is insufficient to conclusively determine if they cause schizophrenia and, if they do, which of the deleted genes are responsible. We propose to determine the DNA sequence of the entire 5.3 Mb delineated by these three deletions in 1,000 individuals with schizophrenia and 1,000 controls to look for both common and rare variants in the deleted regions. The individuals to be sequenced will be chosen from the Portuguese Island Cohort (PIC). The DNA sequence data will be analyzed using logistic regression to determine regions of increased genetic variation in cases as compared to controls. These regions will then be genotyped in a larger sample of up to 20,000 cases and controls to determine which genes/regions in the deleted regions play a causative role in the development of schizophrenia.

Public Health Relevance

Schizophrenia is a severe mental illness that afflicts approximately one percent of the world's population. Although it is clear that approximately a half of the liability to develop the disorder is genetic, few genes have been unequivocally implicated in the etiology of the disorder. Recent data from a large (~3,000 cases and 3,000 controls) study of copy number variations in schizophrenia found evidence for three rare deletions on chromosomes 1q, 15q and 22p that may cause schizophrenia.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01MH086873-05
Application #
8647001
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Addington, Anjene M
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Southern California
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90089