Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling

Rapid cycling (RC) burdens bipolar disorder (BD) patients further by causing more severe disability and increased suicidality. Because diagnosing RC can be challenging, RC patients are at risk of rapid decline due to delayed suitable treatment. Here, we aimed to identify the differences in the circu...

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Autores principales:	Ada Man-Choi Ho, Stacey J. Winham, Bryan M. McCauley, Marija Kundakovic, Keith D. Robertson, Zhifu Sun, Tamas Ordog, Lauren M. Webb, Mark A. Frye, Marin Veldic
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bipolar disorder rapid cycling plasma cell-free DNA methylomics microarray Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/043abd74a9934f2b9b733de5c9728bc4
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spelling	oai:doaj.org-article:043abd74a9934f2b9b733de5c9728bc42021-12-01T18:48:38ZPlasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling1662-453X10.3389/fnins.2021.774037https://doaj.org/article/043abd74a9934f2b9b733de5c9728bc42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.774037/fullhttps://doaj.org/toc/1662-453XRapid cycling (RC) burdens bipolar disorder (BD) patients further by causing more severe disability and increased suicidality. Because diagnosing RC can be challenging, RC patients are at risk of rapid decline due to delayed suitable treatment. Here, we aimed to identify the differences in the circulating cell-free DNA (cfDNA) methylome between BD patients with and without RC. The cfDNA methylome could potentially be developed as a diagnostic test for BD RC. We extracted cfDNA from plasma samples of BD1 patients (46 RC and 47 non-RC). cfDNA methylation levels were measured by 850K Infinium MethylationEPIC array. Principal component analysis (PCA) was conducted to assess global differences in methylome. cfDNA methylation levels were compared between RC groups using a linear model adjusted for age and sex. PCA suggested differences in methylation profiles between RC groups (p = 0.039) although no significant differentially methylated probes (DMPs; q > 0.15) were found. The top four CpG sites which differed between groups at p < 1E-05 were located in CGGPB1, PEX10, NR0B2, and TP53I11. Gene set enrichment analysis (GSEA) on top DMPs (p < 0.05) showed significant enrichment of gene sets related to nervous system tissues, such as neurons, synapse, and glutamate neurotransmission. Other top notable gene sets were related to parathyroid regulation and calcium signaling. To conclude, our study demonstrated the feasibility of utilizing a microarray method to identify circulating cfDNA methylation sites associated with BD RC and found the top differentially methylated CpG sites were mostly related to the nervous system and the parathyroid.Ada Man-Choi HoStacey J. WinhamBryan M. McCauleyMarija KundakovicKeith D. RobertsonZhifu SunTamas OrdogLauren M. WebbMark A. FryeMarin VeldicFrontiers Media S.A.articlebipolar disorderrapid cyclingplasmacell-free DNAmethylomicsmicroarrayNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bipolar disorder rapid cycling plasma cell-free DNA methylomics microarray Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	bipolar disorder rapid cycling plasma cell-free DNA methylomics microarray Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Ada Man-Choi Ho Stacey J. Winham Bryan M. McCauley Marija Kundakovic Keith D. Robertson Zhifu Sun Tamas Ordog Lauren M. Webb Mark A. Frye Marin Veldic Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling
description	Rapid cycling (RC) burdens bipolar disorder (BD) patients further by causing more severe disability and increased suicidality. Because diagnosing RC can be challenging, RC patients are at risk of rapid decline due to delayed suitable treatment. Here, we aimed to identify the differences in the circulating cell-free DNA (cfDNA) methylome between BD patients with and without RC. The cfDNA methylome could potentially be developed as a diagnostic test for BD RC. We extracted cfDNA from plasma samples of BD1 patients (46 RC and 47 non-RC). cfDNA methylation levels were measured by 850K Infinium MethylationEPIC array. Principal component analysis (PCA) was conducted to assess global differences in methylome. cfDNA methylation levels were compared between RC groups using a linear model adjusted for age and sex. PCA suggested differences in methylation profiles between RC groups (p = 0.039) although no significant differentially methylated probes (DMPs; q > 0.15) were found. The top four CpG sites which differed between groups at p < 1E-05 were located in CGGPB1, PEX10, NR0B2, and TP53I11. Gene set enrichment analysis (GSEA) on top DMPs (p < 0.05) showed significant enrichment of gene sets related to nervous system tissues, such as neurons, synapse, and glutamate neurotransmission. Other top notable gene sets were related to parathyroid regulation and calcium signaling. To conclude, our study demonstrated the feasibility of utilizing a microarray method to identify circulating cfDNA methylation sites associated with BD RC and found the top differentially methylated CpG sites were mostly related to the nervous system and the parathyroid.
format	article
author	Ada Man-Choi Ho Stacey J. Winham Bryan M. McCauley Marija Kundakovic Keith D. Robertson Zhifu Sun Tamas Ordog Lauren M. Webb Mark A. Frye Marin Veldic
author_facet	Ada Man-Choi Ho Stacey J. Winham Bryan M. McCauley Marija Kundakovic Keith D. Robertson Zhifu Sun Tamas Ordog Lauren M. Webb Mark A. Frye Marin Veldic
author_sort	Ada Man-Choi Ho
title	Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling
title_short	Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling
title_full	Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling
title_fullStr	Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling
title_full_unstemmed	Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling
title_sort	plasma cell-free dna methylomics of bipolar disorder with and without rapid cycling
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/043abd74a9934f2b9b733de5c9728bc4
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Plasma Cell-Free DNA Methylomics of Bipolar Disorder With and Without Rapid Cycling

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