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A MIR4646 associate...
A MIR4646 associated methylation locus is hypomethylated in adolescent depression
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- Boström, Adrian (author)
- Uppsala universitet,Funktionell farmakologi
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- Ciuculete, Diana-Maria (author)
- Uppsala universitet,Funktionell farmakologi
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- Attwood, Misty M. (author)
- Uppsala universitet,Funktionell farmakologi
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- Krattinger, Regina (author)
- Univ Zurich, Univ Zurich Hosp, Dept Clin Pharmacol & Toxicol, Zurich, Switzerland.
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- Nikontovic, Lamia (author)
- Uppsala universitet,Funktionell farmakologi
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- Titova, Olga E (author)
- Uppsala universitet,Funktionell farmakologi
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- Kullak-Ublick, Gerd A. (author)
- Univ Zurich, Univ Zurich Hosp, Dept Clin Pharmacol & Toxicol, Zurich, Switzerland.
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- Mwinyi, Jessica (author)
- Uppsala universitet,Funktionell farmakologi
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- Schiöth, Helgi B. (author)
- Uppsala universitet,Funktionell farmakologi
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 220, s. 117-128
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- Background: Studies of epigenetics and transcriptional activity in adolescents may provide knowledge about possible preventive strategies of depression. 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. 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). Limitations: MIR4646 was not differentially expressed in a subset of samples with adolescent depression measured by qRT-PCR measurements. 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Keyword
- MIR4646
- Methylome-wide association study
- Adolescent depression
- Omega-3
- MicroRNA
Publication and Content Type
- ref (subject category)
- art (subject category)
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