School of Medicine Publications and Presentations
Document Type
Article
Publication Date
3-16-2021
Abstract
Background: Schizophrenia (SCZ) and bipolar disorder (BIP) are debilitating neuropsychiatric disorders, collectively affecting 2% of the world's population. Recognizing the major impact of these psychiatric disorders on the psychosocial function of more than 200 000 US Veterans, the Department of Veterans Affairs (VA) recently completed genotyping of more than 8000 veterans with SCZ and BIP in the Cooperative Studies Program (CSP) #572.
Methods: We performed genome-wide association studies (GWAS) in CSP #572 and benchmarked the predictive value of polygenic risk scores (PRS) constructed from published findings. We combined our results with available summary statistics from several recent GWAS, realizing the largest and most diverse studies of these disorders to date.
Results: Our primary GWAS uncovered new associations between CHD7 variants and SCZ, and novel BIP associations with variants in Sortilin Related VPS10 Domain Containing Receptor 3 (SORCS3) and downstream of PCDH11X. Combining our results with published summary statistics for SCZ yielded 39 novel susceptibility loci including CRHR1, and we identified 10 additional findings for BIP (28 326 cases and 90 570 controls). PRS trained on published GWAS were significantly associated with case-control status among European American (P < 10-30) and African American (P < .0005) participants in CSP #572.
Conclusions: We have demonstrated that published findings for SCZ and BIP are robustly generalizable to a diverse cohort of US veterans. Leveraging available summary statistics from GWAS of global populations, we report 52 new susceptibility loci and improved fine-mapping resolution for dozens of previously reported associations.
Recommended Citation
Bigdeli, T. B., Fanous, A. H., Li, Y., Rajeevan, N., Sayward, F., Genovese, G., Gupta, R., Radhakrishnan, K., Malhotra, A. K., Sun, N., Lu, Q., Hu, Y., Li, B., Chen, Q., Mane, S., Miller, P., Cheung, K. H., Gur, R. E., Greenwood, T. A., Braff, D. L., … Harvey, P. D. (2021). Genome-Wide Association Studies of Schizophrenia and Bipolar Disorder in a Diverse Cohort of US Veterans. Schizophrenia bulletin, 47(2), 517–529. https://doi.org/10.1093/schbul/sbaa133
Publication Title
Schizophrenia bulletin
DOI
Schizophrenia bulletin
Academic Level
faculty
Mentor/PI Department
Psychiatry
Comments
Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2020.
This work is written by (a) US Government employee(s) and is in the public domain in the US.