Genome-wide DNA methylation and gene expression analyses in monozygotic twins identify potential biomarkers of depression
Depression is currently the leading cause of disability around the world. We conducted an epigenome-wide association study (EWAS) in a sample of 58 depression score-discordant monozygotic twin pairs, aiming to detect specific epigenetic variants potentially related to depression and further integrat...
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Published in | Translational psychiatry Vol. 11; no. 1; p. 416 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
02.08.2021
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Depression is currently the leading cause of disability around the world. We conducted an epigenome-wide association study (EWAS) in a sample of 58 depression score-discordant monozygotic twin pairs, aiming to detect specific epigenetic variants potentially related to depression and further integrate with gene expression profile data. Association between the methylation level of each CpG site and depression score was tested by applying a linear mixed effect model. Weighted gene co-expression network analysis (WGCNA) was performed for gene expression data. The association of DNA methylation levels of 66 CpG sites with depression score reached the level of
P
< 1 × 10
−4
. These top CpG sites were located at 34 genes, especially
PTPRN2
,
HES5
,
GATA2
,
PRDM7
, and
KCNIP1
. Many ontology enrichments were highlighted, including Notch signaling pathway, Huntington disease, p53 pathway by glucose deprivation, hedgehog signaling pathway, DNA binding, and nucleic acid metabolic process. We detected 19 differentially methylated regions (DMRs), some of which were located at
GRIK2
,
DGKA
, and
NIPA2
. While integrating with gene expression data,
HELZ2
,
PTPRN2
,
GATA2
, and
ZNF624
were differentially expressed. In WGCNA, one specific module was positively correlated with depression score (
r
= 0.62,
P
= 0.002). Some common genes (including
BMP2
,
PRDM7
,
KCNIP1
, and
GRIK2
) and enrichment terms (including complement and coagulation cascades pathway, DNA binding, neuron fate specification, glial cell differentiation, and thyroid gland development) were both identified in methylation analysis and WGCNA. Our study identifies specific epigenetic variations which are significantly involved in regions, functional genes, biological function, and pathways that mediate depression disorder. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2158-3188 2158-3188 |
DOI: | 10.1038/s41398-021-01536-y |