Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder
Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder
Abstract 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 predictor 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.
Mirza Salahudeen、Fries Gabriel R.、Topolski Natasha、Gaine Marie E.、Walss-Bass Consuelo、Soares Jair C.、Blumberg Hilary P.、Richards Jenny Gringer、Wemmie John A.、Kov¨￠cs Emese H.C.、Rubinstein Alexandre、Cabrera-Mendoza Brenda、Magnotta Vincent A.、Williams Aislinn J.、Fiedorowicz Jess G.、de Carvalho Lima Camila N.、Del Favero-Campbell Alexandra、Quevedo Joao
Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)||Institute of Child Development, University of MinnesotaTranslational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)||Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences||Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at HoustonTranslational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)||Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesIowa Neuroscience Institute, The University of Iowa.||Pharmaceutical Sciences and Experimental Therapeutics, The University of IowaTranslational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)||Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesTranslational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)||Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences||Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at HoustonDepartment of Psychiatry, Yale School of MedicineDepartment of Radiology, The University of IowaDepartment of Psychiatry, The University of Iowa||Iowa Neuroscience Institute, The University of Iowa.||Department of Veterans Affairs Medical CenterDepartment of Neuroscience and Pharmacology, The University of IowaTranslational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)Department of Psychiatry, Yale School of MedicineDepartment of Radiology, The University of Iowa||Department of Psychiatry, The University of IowaDepartment of Psychiatry, The University of Iowa||Iowa Neuroscience Institute, The University of Iowa.University of Ottawa Brain and Mind Research Institute, Ottawa Hospital Research InstituteTranslational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston , (UTHealth)||Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences||Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston
医学研究方法神经病学、精神病学基础医学
suicide attemptbipolar disorderepigeneticsmethylationbloodbiomarker
Mirza Salahudeen,Fries Gabriel R.,Topolski Natasha,Gaine Marie E.,Walss-Bass Consuelo,Soares Jair C.,Blumberg Hilary P.,Richards Jenny Gringer,Wemmie John A.,Kov¨￠cs Emese H.C.,Rubinstein Alexandre,Cabrera-Mendoza Brenda,Magnotta Vincent A.,Williams Aislinn J.,Fiedorowicz Jess G.,de Carvalho Lima Camila N.,Del Favero-Campbell Alexandra,Quevedo Joao.Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder[EB/OL].(2025-03-28)[2025-06-30].https://www.medrxiv.org/content/10.1101/2023.07.20.23292968.点此复制
评论