Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder

Bigdeli, Tim B.; Barr, Peter B.; Rajeevan, Nallakkandi; Graham, David P.; Li, Yuli; Meyers, Jacquelyn L.; Gorman, Bryan R.; Peterson, Roseann E.; Sayward, Frederick; Radhakrishnan, Krishnan; Natarajan, Sundar; Nielsen, David A.; Wilkinson, Anna V.; Malhotra, Anil K.; Zhao, Hongyu; Brophy, Mary; Shi, Yunling; O’Leary, Timothy J.; Gleason, Theresa; Przygodzki, Ronald; Pyarajan, Saiju; Muralidhar, Sumitra; Gaziano, J. Michael; Huang, Grant D.; Concato, John; Siever, Larry J.; DeLisi, Lynn E.; Kimbrel, Nathan A.; Beckham, Jean C.; Swann, Alan C.; Kosten, Thomas R.; Fanous, Ayman H.; ,; O’Leary, Timothy J.; Gleason, Theresa; Przygodzki, Ronald; Muralidhar, Sumitra; Gaziano, Michael; Huang, Grant D.; Concato, John; DeLisi, Lynn E.; Aslan, Mihaela; Harvey, Philip D.

doi:10.1038/s41380-024-02472-1

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…Both of the validation cohorts have been previously described, in detail. Briefly, the "Cooperative Studies Program" (CSP) #572 cohort, entitled "Genetics of Functional Disability in Schizophrenia and Bipolar Illness Validation" was collected to evaluate genetic and other characteristics of veterans with severe psychiatric illness (39,40). Participants in CSP #572 (N = 9,151, 86.2% male) universally received C-SSRS screening during the baseline diagnostic interview.…”

Section: Suicide Attempt Icd List Validationmentioning

confidence: 99%

Defining Suicidal Thought and Behavior Phenotypes for Genetic Studies

Monson,

Colbert,

Andreassen

et al. 2024

Preprint

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Background: Standardized definitions of suicidality phenotypes, including suicidal ideation (SI), attempt (SA), and death (SD) are a critical step towards improving understanding and comparison of results in suicide research. The complexity of suicidality contributes to heterogeneity in phenotype definitions, impeding evaluation of clinical and genetic risk factors across studies and efforts to combine samples within consortia. Here, we present expert and data-supported recommendations for defining suicidality and control phenotypes to facilitate merging current/legacy samples with definition variability and aid future sample creation. Methods: A subgroup of clinician researchers and experts from the Suicide Workgroup of the Psychiatric Genomics Consortium (PGC) reviewed existing PGC definitions for SI, SA, SD, and control groups and generated preliminary consensus guidelines for instrument-derived and international classification of disease (ICD) data. ICD lists were validated in two independent datasets (N = 9,151 and 12,394). Results: Recommendations are provided for evaluated instruments for SA and SI, emphasizing selection of lifetime measures phenotype-specific wording. Recommendations are also provided for defining SI and SD from ICD data. As the SA ICD definition is complex, SA code list recommendations were validated against instrument results with sensitivity (range = 15.4% to 80.6%), specificity (range = 67.6% to 97.4%), and positive predictive values (range = 0.59-0.93) reported. Conclusions: Best-practice guidelines are presented for the use of existing information to define SI/SA/SD in consortia research. These proposed definitions are expected to facilitate more homogeneous data aggregation for genetic and multisite studies. Future research should involve refinement, improved generalizability, and validation in diverse populations.

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Section: Suicide Attempt Icd List Validationmentioning

confidence: 99%

Defining Suicidal Thought and Behavior Phenotypes for Genetic Studies

Monson,

Colbert,

Andreassen

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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Distinguishing clinical and genetic risk factors for suicidal ideation and behavior in a diverse hospital population

Colbert,

Lepow,

Fennessy

et al. 2024

Preprint

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Suicidal ideation (SI) and behavior (SB) are major public health concerns, but risk factors for their development and progression are poorly understood. We used ICD codes and a natural language processing algorithm to identify individuals in a hospital biobank with SI-only, SB, and controls without either. We compared the profiles of SB and SI-only patients to controls, and each other, using phenome-wide association studies (PheWAS) and polygenic risk scores (PRS). PheWAS identified many risk factors for SB and SI-only, plus specific psychiatric disorders which may be involved in progression from SI-only to SB. PRS for suicide attempt were only associated with SB, and even after accounting for psychiatric disorder PRS. SI PRS were only associated with SI-only, although not after accounting for psychiatric disorder PRS. These findings advance understanding of distinct genetic and clinical risk factors for SB and SI-only, which will aid in early detection and intervention efforts.

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The Impact of Selection Bias on Genetic Prediction Using the Bipolar Polygenic Risk Score in First-Admission Psychosis

Jonas,

Asim,

Yang

et al. 2024

Preprint

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Polygenic risk scores (PRS) have potential utility as biomarkers of psychiatric disorders. However, while the schizophrenia (SZ) PRS has been consistently associated with case-control status and a more severe course of illness, the associations between the bipolar (BP) PRS and markers of bipolar disorder vary considerably between studies, with studies of population and case-control samples identifying many effects that cannot be replicated in case-only analyses. These analyses demonstrate that the heterogeneity in studies of the BP PRS is driven by selection bias. Specifically, selecting samples on the basis of diagnostic status or other phenotypes associated with genetic risk attenuates the correlation between the BP and SZ PRS. In such high-severity samples, while the SZ PRS predicts poor outcomes, the BP PRS predicts better outcomes. These findings highlight the importance of understanding the impact of selection bias in translational research evaluating PRS as biomarkers of psychiatric disorders, particularly when the intended application is populations enriched for high levels of genetic risk.

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Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder

Cited by 3 publications

References 57 publications

Defining Suicidal Thought and Behavior Phenotypes for Genetic Studies

Defining Suicidal Thought and Behavior Phenotypes for Genetic Studies

Distinguishing clinical and genetic risk factors for suicidal ideation and behavior in a diverse hospital population

The Impact of Selection Bias on Genetic Prediction Using the Bipolar Polygenic Risk Score in First-Admission Psychosis

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