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

Salahudeen Mirza; Camila N. C. Lima; Alexandra Del Favero-Campbell; Alexandre Rubinstein; Natasha Topolski; Brenda Cabrera-Mendoza; Emese H. C. Kovács; Hilary P. Blumberg; Jenny Gringer Richards; Aislinn J. Williams; John A. Wemmie; Vincent A. Magnotta; Jess G. Fiedorowicz; Marie E. Gaine; Consuelo Walss-Bass; Joao Quevedo; Jair C. Soares; Gabriel R. Fries

doi:10.1038/s41398-024-02760-y

Back

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

Journal article

Open access

Peer reviewed

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

Salahudeen Mirza, Camila N. C. Lima, Alexandra Del Favero-Campbell, Alexandre Rubinstein, Natasha Topolski, Brenda Cabrera-Mendoza, Emese H. C. Kovács, Hilary P. Blumberg, Jenny Gringer Richards, Aislinn J. Williams, …

Translational psychiatry, Vol.14(1), 70

01/31/2024

DOI: 10.1038/s41398-024-02760-y

PMCID: PMC10831084

PMID: 38296944

Files and links (1)

url

https://doi.org/10.1038/s41398-024-02760-yView

Published (Version of record) Open Access

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 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.

Details

Title: Subtitle: Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder
Creators: Salahudeen Mirza - The University of Texas Health Science Center at Houston
Camila N. C. Lima - The University of Texas Health Science Center at Houston
Alexandra Del Favero-Campbell - The University of Texas Health Science Center at Houston
Alexandre Rubinstein - The University of Texas Health Science Center at Houston
Natasha Topolski - The University of Texas Health Science Center at Houston
Brenda Cabrera-Mendoza - Yale School of Medicine
Emese H. C. Kovács - University of Iowa
Hilary P. Blumberg - Yale University
Jenny Gringer Richards - University of Iowa
Aislinn J. Williams - 200 Hawkins Dr, 52242 Iowa City, IA USA 169 Newton Rd, 52242 Iowa City, IA USA
John A. Wemmie - University of Iowa
Vincent A. Magnotta - University of Iowa
Jess G. Fiedorowicz - University of Ottawa
Marie E. Gaine - University of Iowa
Consuelo Walss-Bass - The University of Texas Health Science Center at Houston
Joao Quevedo - The University of Texas Health Science Center at Houston
Jair C. Soares - The University of Texas Health Science Center at Houston
Gabriel R. Fries - The University of Texas Health Science Center at Houston
Resource Type: Journal article
Publication Details: Translational psychiatry, Vol.14(1), 70
DOI: 10.1038/s41398-024-02760-y
PMID: 38296944
PMCID: PMC10831084
NLM abbreviation: Transl Psychiatry
eISSN: 2158-3188
Publisher: Nature Publishing Group UK
Grant note: DOI: 10.13039/100000025, name: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health, award: K01 MH121580, R01MH125838, R01MH111578, R01MH125838, R01MH111578; DOI: 10.13039/100001455, name: American Foundation for Suicide Prevention, award: YIG-0-066-20; DOI: 10.13039/100000026, name: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse, award: R01DA052953
Language: English
Date published: 01/31/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Molecular Physiology and Biophysics; Psychiatry; Epidemiology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Neurosurgery
Record Identifier: 9984555560102771

Metrics

18 Record Views

16 Times Cited - Web of Science