Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder

Lima, Camila N. C.; Kovács, Emese H. C.; Mirza, Salahudeen; Favero-Campbell, Alexandra Del; Diaz, Alexandre Paim; Quevedo, Joao L De; Argue, Benney M R; Richards, Jenny Gringer; Williams, Ann E.; Wemmie, John A.; Magnotta, Vincent A.; Fiedorowicz, Jess G.; Soares, Jair C.; Gaine, Marie E.; Fries, Gabriel R.

doi:10.1038/s41386-023-01557-9

Cited by 9 publications

(7 citation statements)

References 86 publications

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“…This sample has been previously described [ 22 ]. One hundred and sixty-one adults with BD (79 BD/non-SA, 84 BD/SA) and 76 non-psychiatric controls without a lifetime history of SA (CON) were recruited at the Center of Excellence in Mood Disorders, Houston, TX.…”

Section: Methodsmentioning

confidence: 99%

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

Mirza,

Lima,

Del Favero-Campbell

et al. 2024

Transl Psychiatry

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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.

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Section: Methodsmentioning

confidence: 99%

“…This sample has been previously described [ 22 ]. Ninety-five adults with BD (48 BD/SA, 47 BD/non-SA) were recruited through the IRB-approved Iowa Neuroscience Institute Bipolar Disorder Research Program of Excellence (BD-RPOE).…”

Section: Methodsmentioning

confidence: 99%

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

Mirza,

Lima,

Del Favero-Campbell

et al. 2024

Transl Psychiatry

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“…The Iowa Neuroscience Institute's Bipolar Disorder Research Program of Excellence (BD-RPOE) recruited participants, after University of Iowa Institutional Review Board approval, for this study as previously described [9,11,[20][21][22][23][24][25][26][27][28]. Written informed consent was provided by all participants and most also provided a blood sample for epi/genetic analyses.…”

Section: Participants and Sample Collectionmentioning

confidence: 99%

“…A targeted sequencing study focused on suicide death investigated over 3.7 million CpG sites and reported hypomethylation at Rho Guanine Nucleotide Exchange Factor 38 ( ARHGEF38) [10]. More recently, studies have shown that epigenetic aging is increased in individuals with BD and a history of suicide attempts [11]. Despite interesting and biologically relevant findings, many DNA methylation changes associated with suicide in BD have yet to be replicated in independent cohorts.…”

Section: Introductionmentioning

confidence: 99%

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Investigating the relationship between DNA methylation, genetic variation, and suicide attempt in bipolar disorder

Alrfooh,

Casten,

Richards

et al. 2024

Preprint

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Individuals with bipolar disorder are at increased risk for suicide, and this can be influenced by a range of biological, clinical, and environmental risk factors. Biological components associated with suicide include DNA modifications that lead to changes in gene expression. Common genetic variation and DNA methylation changes are some of the most frequent types of DNA findings associated with an increased risk for suicidal behavior. Importantly, the interplay between genetic predisposition and DNA methylation patterns is becoming more prevalent in genetic studies. We hypothesized that DNA methylation patterns in specific loci already genetically associated with suicide would be altered in individuals with bipolar disorder and a history of suicide attempt. To test this hypothesis, we searched the literature to identify common genetic variants (N=34) previously associated with suicidal thoughts and behaviors in individuals with bipolar disorder. We then created a customized sequencing panel that covered our chosen genomic loci. We profiled DNA methylation patterns from blood samples collected from bipolar disorder participants with suicidal behavior (N=55) and without suicidal behavior (N=51). We identified seven differentially methylated CpG sites and five differentially methylated regions between the two groups. Additionally, we found that DNA methylation changes inMIFandCACNA1Cwere associated with lethality or number of suicide attempts. Finally, we identified three meQTLs inSIRT1,IMPA2, andINPP1. This study illustrates that DNA methylation is altered in individuals with bipolar disorder and a history of suicide attempts in regions known to harbor suicide-related variants.

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Elevated senescence-associated secretory phenotype index in late-life bipolar disorder

Tessema,

Diniz,

Vieira

et al. 2024

Journal of Affective Disorders

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Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder

Cited by 9 publications

References 86 publications

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

Investigating the relationship between DNA methylation, genetic variation, and suicide attempt in bipolar disorder

Elevated senescence-associated secretory phenotype index in late-life bipolar disorder

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