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A MIR4646 associated methylation locus is hypomethylated in adolescent depression.
- Source :
-
Journal of affective disorders [J Affect Disord] 2017 Oct 01; Vol. 220, pp. 117-128. Date of Electronic Publication: 2017 May 17. - Publication Year :
- 2017
-
Abstract
- Background: Studies of epigenetics and transcriptional activity in adolescents may provide knowledge about possible preventive strategies of depression.<br />Methods: We present a methylome-wide association study (MWAS) and cohort validation analysis of depression in adolescents, in two separate cohorts: discovery (n=93) and validation data set 1 (n=78). The genome-wide methylation pattern was measured from whole blood using the Illumina 450K array. A second validation cohort, validation data set 2, consists of post-mortem brain biopsies from depressed adults (n=58). We performed a MWAS by robust multiple linear regressions of methylation to a modified risk-score assessment of depression. Methylation levels of candidate CpG sites were correlated with expression levels of the associated gene in an independent cohort of 11 healthy volunteers.<br />Results: The methylation state of two CpG sites reliably predicted ratings of depression in adolescents (cg13227623 and cg04102384) (p<10E-06). Cohort validation analysis confirmed cg04102384 - located in the promoter region of microRNA 4646 (MIR4646) - to be hypomethylated in both validation data set 1 and validation data set 2 (p<0.05). Cg04102384 was inversely correlated to expression levels of MIR4646-3p in healthy controls (p<0.05).<br />Limitations: MIR4646 was not differentially expressed in a subset of samples with adolescent depression measured by qRT-PCR measurements.<br />Conclusion: We identify a specific MIR4646 associated epigenetic risk site to be associated with depression in adolescents. Cg04102384 putatively regulates gene expression of MIR4646-3p. Target gene prediction and gene set overrepresentation analysis revealed involvement of this miRNA in fatty acid elongation, a process related to omega-3 fatty acids, previously associated with depression.<br /> (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Acetyltransferases genetics
Adolescent
Cohort Studies
CpG Islands genetics
Epigenomics
Fatty Acid Elongases
Fatty Acids, Omega-3 genetics
Female
Gene Expression
Genome-Wide Association Study
Humans
Male
Real-Time Polymerase Chain Reaction
DNA Methylation
Depressive Disorder genetics
Epigenesis, Genetic
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2517
- Volume :
- 220
- Database :
- MEDLINE
- Journal :
- Journal of affective disorders
- Publication Type :
- Academic Journal
- Accession number :
- 28618313
- Full Text :
- https://doi.org/10.1016/j.jad.2017.05.017