Abstract
F41. STEPS TOWARD A COMBINED CLINICAL-EPIGENETIC PREDICTOR OF SUICIDE ATTEMPT RISK IN BIPOLAR DISORDER: PRELIMINARY INSIGHTS FROM CROSS-SECTIONAL AND RETROSPECTIVE ASSESSMENTS
European neuropsychopharmacology, Vol.75, pp.S242-S243
10/2023
DOI: 10.1016/j.euroneuro.2023.08.429
Abstract
Bipolar disorder (BD) is associated with elevated risk for suicide attempt (SA). Understanding the underlying mechanisms of SA risk in BD is critical for developing novel preventive and interventional strategies. Epigenetic modifications may capture experiential and genetic contributions. We conducted an epigenome-wide association study (EWAS) of SA history in BD using DNA from peripheral blood. We tested the SA classification capability of the top DNA methylation markers within our original cohort as well as an independent replication cohort. Additionally, we combined the information from the DNA methylation markers with clinical measures previously associated with SA history in mood disorder to assess whether integrating the levels of analysis improved ability to detect SA history.
The discovery cohort consisted of 162 adults with BD (79 BD without SA, 84 BD with SA) from the University of Texas Health Science Center at Houston. DNA was isolated from the buffy coat of peripheral blood, and DNA methylation measurement was conducted using the Illumina Infinium EPICMethylation BeadChip version 1.0. The EWAS was conducted using R packages minfi and limma and identified patterns of differential methylation associated with SA history. The methylation markers which survived a false discovery rate correction threshold of q = 0.05 were tested for their SA classification capability using generalized linear models and the area under the curve (AUC) of the receiver operating curve (ROC). The methylation markers were tested both independently and in conjunction with clinical measures previously associated with SA history in mood disorders (age, sex, number of previous hospitalisations for depression, history of psychosis, cocaine dependence, and post-traumatic stress disorder). Finally, the AUC analyses were repeated in a replication cohort of 95 adults with BD (47 BD without SA, 48 BD with SA) from the University of Iowa.
EWAS in the discovery cohort revealed six sites which were significantly associated with SA history. In the discovery cohort, the AUC was 83.7% (95% CI = 77.5-89.9%) for classification based on these sites alone, 77.9% (95% CI = 70.6-85.3%) for classification based on clinical measures alone, and 88.8% (95% CI = 83.8-93.8%) for classification on combined methylation and clinical measures. In the replication cohort, the AUC was 67.6% (95% CI = 56.6-78.5%) for classification based on the six sites alone, 77.6% (95% CI = 68.2-86.9%) for classification based on clinical measures alone, and 82.1% (95% CI = 73.6-90.5%) for classification on combined methylation and clinical measures.
Results from this EWAS of SA in BD suggest that not only can information from DNA methylation measurement potentially identify patterns of risk for SA, but it can also be integrated with information from clinical interviews in a complementary fashion. This preliminary work sets a foundation for further investigation of multi-level markers of risk for SA and BD which could eventually improve ascertainment, prediction, and early intervention.
Details
- Title: Subtitle
- F41. STEPS TOWARD A COMBINED CLINICAL-EPIGENETIC PREDICTOR OF SUICIDE ATTEMPT RISK IN BIPOLAR DISORDER: PRELIMINARY INSIGHTS FROM CROSS-SECTIONAL AND RETROSPECTIVE ASSESSMENTS
- Creators
- Salahudeen Mirza - Yale School of MedicineCamila Nayane de Carvalho Lima - The University of Texas Health Science Center at HoustonAlexandra Del Favero-Campbell - Dalhousie UniversityAlexandre Rubinstein - The University of Texas Health Science Center at HoustonNatasha Topolski - The University of Texas Health Science Center at HoustonBrenda Cabrera-Mendoza - Yale School of MedicineEmese Kovács - The University of IowaJenny Gringer Richards - University of IowaAislinn Williams - University of IowaJohn Wemmie - The University of IowaConsuelo Walss-Bass - The University of Texas Health Science Center at HoustonJoao Quevedo - The University of Texas Health Science Center at HoustonMarie Gaine - University of IowaJair Soares - The University of Texas Health Science Center at HoustonGabriel Fries - The University of Texas Health Science Center at Houston
- Resource Type
- Abstract
- Publication Details
- European neuropsychopharmacology, Vol.75, pp.S242-S243
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.euroneuro.2023.08.429
- ISSN
- 0924-977X
- eISSN
- 1873-7862
- Language
- English
- Date published
- 10/2023
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Radiology; Molecular Physiology and Biophysics; Neurosurgery; Iowa Neuroscience Institute; Psychiatry
- Record Identifier
- 9984476554802771
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