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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8877131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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