A DNA methylation signature discriminates between excellent and non-response to lithium in patients with bipolar disorder type 1 - Archive ouverte HAL Access content directly
Journal Articles Scientific Reports Year : 2020

A DNA methylation signature discriminates between excellent and non-response to lithium in patients with bipolar disorder type 1

(1) , (2) , (3) , (2) , (2) , (1, 4, 5, 6) , (1, 4, 5, 6)
1
2
3
4
5
6

Abstract

Lithium (Li) is the cornerstone maintenance treatment for bipolar disorders (BD), but response rates are highly variable. To date, no clinical or biological marker is available to reliably define eligibility criteria for a maintenance treatment with Li. We examined whether the prophylactic response to Li (assessed retrospectively) is associated with distinct blood DNA methylation profiles. Bisulfite-treated total blood DNA samples from individuals with BD type 1 (15 excellent-responders (LiERs) versus 11 non-responders (LiNRs)) were used for targeted enrichment of CpG rich genomic regions followed by high-resolution next-generation sequencing to identify differentially methylated regions (DMRs). After controlling for potential confounders we identified 111 DMRs that significantly differ between LiERs and LiNRs with a significant enrichment in neuronal cell components. Logistic regression and receiver operating curves identified a combination of 7 DMRs with a good discriminatory power for response to Li (Area Under the Curve 0.806). Annotated genes associated with these DMRs include Eukaryotic Translation Initiation Factor 2B Subunit Epsilon (EIF2B5), Von Willebrand Factor A Domain Containing 5B2 (VWA5B2), Ral GTPase Activating Protein Catalytic Alpha Subunit 1 (RALGAPA1). Although preliminary and deserving replication, these results suggest that biomarkers of response to Li may be identified through peripheral epigenetic measures.
Fichier principal
Vignette du fichier
s41598-020-69073-0.pdf (1.31 Mo) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

inserm-02937821 , version 1 (14-09-2020)

Identifiers

Cite

Cynthia Marie-Claire, François-Xavier Lejeune, Emeline Mundwiller, Damien Ulveling, Ivan Moszer, et al.. A DNA methylation signature discriminates between excellent and non-response to lithium in patients with bipolar disorder type 1. Scientific Reports, 2020, 10 (1), pp.12239. ⟨10.1038/s41598-020-69073-0⟩. ⟨inserm-02937821⟩
49 View
67 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More