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Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study

Response to lithium (Li) is highly variable in bipolar disorders (BD) and no clinical or biological predictors of long-term response have been validated to date. Using a genome-wide methylomic approach (SeqCapEpi), we previously identified seven differentially methylated regions (DMRs) that discrimi...

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Autores principales: Marie-Claire, Cynthia, Courtin, Cindie, Bellivier, Frank, Scott, Jan, Etain, Bruno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877131/
https://www.ncbi.nlm.nih.gov/pubmed/35215246
http://dx.doi.org/10.3390/ph15020133
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author Marie-Claire, Cynthia
Courtin, Cindie
Bellivier, Frank
Scott, Jan
Etain, Bruno
author_facet Marie-Claire, Cynthia
Courtin, Cindie
Bellivier, Frank
Scott, Jan
Etain, Bruno
author_sort Marie-Claire, Cynthia
collection PubMed
description Response to lithium (Li) is highly variable in bipolar disorders (BD) and no clinical or biological predictors of long-term response have been validated to date. Using a genome-wide methylomic approach (SeqCapEpi), we previously identified seven differentially methylated regions (DMRs) that discriminated good from non-responders (prophylactic response phenotype defined using the “Alda” scale). This study is a proof of transferability from bench to bedside of this epigenetic signature. For this purpose, we used Methylation Specific High-Resolution Melting (MS-HRM), a PCR based method that can be implemented in any medical laboratory at low cost and with minimal equipment. In 23 individuals with BD, MS-HRM measures of three out of seven DMRs were technically feasible and consistencies between SeqCapEpi and MS-HRM-measures were moderate to high. In an extended sample of individuals with BD (n = 70), the three MS-HRM-measured DMRs mainly predicted nonresponse, with AUC between 0.70–0.80 according to different definitions of the phenotype (Alda- or machine-learning-based definitions). Classification tree analyses further suggested that the MS-HRM-measured DMRs correctly classified up to 84% of individuals as good or non-responders. This study suggested that epigenetic biomarkers, identified in a retrospective sample, accurately discriminate non-responders from responders to Li and may be transferrable to routine practice.
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spelling pubmed-88771312022-02-26 Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study Marie-Claire, Cynthia Courtin, Cindie Bellivier, Frank Scott, Jan Etain, Bruno Pharmaceuticals (Basel) Article Response to lithium (Li) is highly variable in bipolar disorders (BD) and no clinical or biological predictors of long-term response have been validated to date. Using a genome-wide methylomic approach (SeqCapEpi), we previously identified seven differentially methylated regions (DMRs) that discriminated good from non-responders (prophylactic response phenotype defined using the “Alda” scale). This study is a proof of transferability from bench to bedside of this epigenetic signature. For this purpose, we used Methylation Specific High-Resolution Melting (MS-HRM), a PCR based method that can be implemented in any medical laboratory at low cost and with minimal equipment. In 23 individuals with BD, MS-HRM measures of three out of seven DMRs were technically feasible and consistencies between SeqCapEpi and MS-HRM-measures were moderate to high. In an extended sample of individuals with BD (n = 70), the three MS-HRM-measured DMRs mainly predicted nonresponse, with AUC between 0.70–0.80 according to different definitions of the phenotype (Alda- or machine-learning-based definitions). Classification tree analyses further suggested that the MS-HRM-measured DMRs correctly classified up to 84% of individuals as good or non-responders. This study suggested that epigenetic biomarkers, identified in a retrospective sample, accurately discriminate non-responders from responders to Li and may be transferrable to routine practice. MDPI 2022-01-23 /pmc/articles/PMC8877131/ /pubmed/35215246 http://dx.doi.org/10.3390/ph15020133 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marie-Claire, Cynthia
Courtin, Cindie
Bellivier, Frank
Scott, Jan
Etain, Bruno
Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study
title Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study
title_full Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study
title_fullStr Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study
title_full_unstemmed Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study
title_short Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study
title_sort methylomic biomarkers of lithium response in bipolar disorder: a proof of transferability study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877131/
https://www.ncbi.nlm.nih.gov/pubmed/35215246
http://dx.doi.org/10.3390/ph15020133
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