Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorBigdeli, Tim B
Gorman, Bryan R
Peterson, Roseann E
Burstein, David E
Velicu, Vlad I
Malhotra, Anil K
Kosten, Thomas R
O'Leary, Timothy J
Huang, Grant D
Gaziano, J Michael
Fanous, Ayman H
Harvey, Philip D
Journal titleJAMA psychiatry
MetadataShow full item record
AbstractImportance: Serious mental illnesses, including schizophrenia, bipolar disorder, and depression, are heritable, highly multifactorial disorders and major causes of disability worldwide. Objective: To benchmark the penetrance of current neuropsychiatric polygenic risk scores (PRSs) in the Veterans Health Administration health care system and to explore associations between PRS and broad categories of human disease via phenome-wide association studies. Design, setting, and participants: Extensive Veterans Health Administration's electronic health records were assessed from October 1999 to January 2021, and an embedded cohort of 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder were found. The performance of schizophrenia, bipolar disorder, and major depression PRSs were compared in participants of African or European ancestry in the Million Veteran Program (approximately 400 000 individuals), and associations between PRSs and 1650 disease categories based on ICD-9/10 billing codes were explored. Last, genomic structural equation modeling was applied to derive novel PRSs indexing common and disorder-specific genetic factors. Analysis took place from January 2021 to January 2022. Main outcomes and measures: Diagnoses based on in-person structured clinical interviews were compared with ICD-9/10 billing codes. PRSs were constructed using summary statistics from genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Results: Of 707 299 enrolled study participants, 459 667 were genotyped at the time of writing; 84 806 were of broadly African ancestry (mean [SD] age, 58 [12.1] years) and 314 909 were of broadly European ancestry (mean [SD] age, 66.4 [13.5] years). Among 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder, 8962 (95.6%) were correctly identified using ICD-9/10 codes (2 or more). Among those of European ancestry, PRSs were robustly associated with having received a diagnosis of schizophrenia (odds ratio [OR], 1.81 [95% CI, 1.76-1.87]; P < 10-257) or bipolar disorder (OR, 1.42 [95% CI, 1.39-1.44]; P < 10-295). Corresponding effect sizes in participants of African ancestry were considerably smaller for schizophrenia (OR, 1.35 [95% CI, 1.29-1.42]; P < 10-38) and bipolar disorder (OR, 1.16 [95% CI, 1.11-1.12]; P < 10-10). Neuropsychiatric PRSs were associated with increased risk for a range of psychiatric and physical health problems. Conclusions and relevance: Using diagnoses confirmed by in-person structured clinical interviews and current neuropsychiatric PRSs, the validity of an electronic health records-based phenotyping approach in US veterans was demonstrated, highlighting the potential of PRSs for disentangling biological and mediated pleiotropy.
CitationBigdeli TB, Voloudakis G, Barr PB, Gorman BR, Genovese G, Peterson RE, Burstein DE, Velicu VI, Li Y, Gupta R, Mattheisen M, Tomasi S, Rajeevan N, Sayward F, Radhakrishnan K, Natarajan S, Malhotra AK, Shi Y, Zhao H, Kosten TR, Concato J, O'Leary TJ, Przygodzki R, Gleason T, Pyarajan S, Brophy M, Huang GD, Muralidhar S, Gaziano JM, Aslan M, Fanous AH, Harvey PD, Roussos P; Cooperative Studies Program (CSP) #572 and Million Veteran Program (MVP). Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System. JAMA Psychiatry. 2022 Sep 14. doi: 10.1001/jamapsychiatry.2022.2742. Epub ahead of print. PMID: 36103194.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International
- Role of Polygenic Risk Score in the Familial Transmission of Bipolar Disorder in Youth.
- Authors: Birmaher B, Hafeman D, Merranko J, Zwicker A, Goldstein B, Goldstein T, Axelson D, Monk K, Hickey MB, Sakolsky D, Iyengar S, Diler R, Nimgaonkar V, Uher R
- Issue date: 2022 Feb 1
- Polygenic Risk of Psychiatric Disorders Exhibits Cross-trait Associations in Electronic Health Record Data From European Ancestry Individuals.
- Authors: Kember RL, Merikangas AK, Verma SS, Verma A, Judy R, Regeneron Genetics Center, Damrauer SM, Ritchie MD, Rader DJ, Bućan M
- Issue date: 2021 Feb 1
- Post-partum psychosis and its association with bipolar disorder in the UK: a case-control study using polygenic risk scores.
- Authors: Di Florio A, Mei Kay Yang J, Crawford K, Bergink V, Leonenko G, Pardiñas AF, Escott-Price V, Gordon-Smith K, Owen MJ, Craddock N, Jones L, O'Donovan M, Jones I
- Issue date: 2021 Dec
- Polygenetic Risk Scores for Major Psychiatric Disorders Among Schizophrenia Patients, Their First-Degree Relatives, and Healthy Participants.
- Authors: Ohi K, Nishizawa D, Shimada T, Kataoka Y, Hasegawa J, Shioiri T, Kawasaki Y, Hashimoto R, Ikeda K
- Issue date: 2020 Apr 21
- Generalizability of Polygenic Risk Scores for Breast Cancer Among Women With European, African, and Latinx Ancestry.
- Authors: Liu C, Zeinomar N, Chung WK, Kiryluk K, Gharavi AG, Hripcsak G, Crew KD, Shang N, Khan A, Fasel D, Manolio TA, Jarvik GP, Rowley R, Justice AE, Rahm AK, Fullerton SM, Smoller JW, Larson EB, Crane PK, Dikilitas O, Wiesner GL, Bick AG, Terry MB, Weng C
- Issue date: 2021 Aug 2