Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder.

Autor: Mirza S; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA.; Institute of Child Development, University of Minnesota, 55455, Minneapolis, MN, USA.; Department of Psychiatry, Yale School of Medicine, 06510, New Haven, CT, USA., Lima CNC; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA., Del Favero-Campbell A; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA., Rubinstein A; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA., Topolski N; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA.; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 77054, Houston, TX, USA., Cabrera-Mendoza B; Department of Psychiatry, Yale School of Medicine, 06510, New Haven, CT, USA., Kovács EHC; Department of Neuroscience and Pharmacology, The University of Iowa, 51 Newton Rd, 52242, Iowa City, IA, USA., Blumberg HP; Department of Psychiatry, Yale School of Medicine, 06510, New Haven, CT, USA., Richards JG; Department of Radiology, The University of Iowa, 200 Hawkins Dr, 52242, Iowa City, IA, USA., Williams AJ; Department of Psychiatry, The University of Iowa, 200 Hawkins Dr, 52242, Iowa City, IA, USA.; Iowa Neuroscience Institute, The University of Iowa, 169 Newton Rd, 52242, Iowa City, IA, USA., Wemmie JA; Department of Psychiatry, The University of Iowa, 200 Hawkins Dr, 52242, Iowa City, IA, USA.; Iowa Neuroscience Institute, The University of Iowa, 169 Newton Rd, 52242, Iowa City, IA, USA.; Department of Veterans Affairs Medical Center, Iowa City, IA, USA., Magnotta VA; Department of Radiology, The University of Iowa, 200 Hawkins Dr, 52242, Iowa City, IA, USA.; Department of Psychiatry, The University of Iowa, 200 Hawkins Dr, 52242, Iowa City, IA, USA., Fiedorowicz JG; University of Ottawa Brain and Mind Research Institute, Ottawa Hospital Research Institute, 501 Smyth, K1H 8L6, Ottawa, ON, Canada., Gaine ME; Iowa Neuroscience Institute, The University of Iowa, 169 Newton Rd, 52242, Iowa City, IA, USA.; Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, 180 South Grand Ave, 52242, Iowa City, IA, USA., Walss-Bass C; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA.; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 77054, Houston, TX, USA., Quevedo J; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA.; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 77054, Houston, TX, USA.; Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Rd, 77054, Houston, TX, USA.; Center for Interventional Psychiatry, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, 1941 East Rd, 77054, Houston, TX, USA., Soares JC; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA.; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 77054, Houston, TX, USA.; Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Rd, 77054, Houston, TX, USA., Fries GR; Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, (UTHealth), 77054, Houston, TX, USA. Gabriel.R.Fries@uth.tmc.edu.; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 77054, Houston, TX, USA. Gabriel.R.Fries@uth.tmc.edu.; Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Rd, 77054, Houston, TX, USA. Gabriel.R.Fries@uth.tmc.edu.; Center for Interventional Psychiatry, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, 1941 East Rd, 77054, Houston, TX, USA. Gabriel.R.Fries@uth.tmc.edu.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Jan 31; Vol. 14 (1), pp. 70. Date of Electronic Publication: 2024 Jan 31.
DOI: 10.1038/s41398-024-02760-y
Abstrakt: Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical classifier in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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