Genome-wide Methylomic Analysis of Monozygotic Twins Discordant for Adolescent Depression

Dempster, E.L.; Wong, C.C.Y.; Lester, Kathryn J.; Roberts, S; Burrage, J.; Gregory, Alice M.; Mill, Jonathan and Eley, Thalia C.. 2014. Genome-wide Methylomic Analysis of Monozygotic Twins Discordant for Adolescent Depression. Biological Psychiatry, 76(12), pp. 977-983. ISSN 0006-3223 [Article]

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Abstract or Description

Adolescent depression is a common neuropsychiatric disorder that often continues into adulthood and is associated with a wide range of poor outcomes including suicide. Although numerous studies have looked at genetic markers associated with depression, the role of epigenetic variation remains relatively unexplored.

Monozygotic (MZ) twins were selected from an adolescent twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. There were 18 pairs of MZ twins identified in which one member scored consistently higher (group mean within the clinically significant range) on self-rated depression than the other. We assessed genome-wide patterns of DNA methylation in twin buccal cell DNA using the Infinium HumanMethylation450 BeadChip from Illumina. Quality control and data preprocessing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. The top differentially methylated DMP was successfully validated by bisulfite-pyrosequencing, and identified DMPs were tested in postmortem brain samples obtained from patients with major depressive disorder (n = 14) and matched control subjects (n = 15).

Two reproducible depression-associated DMPs were identified, including the top-ranked DMP that was located within STK32C, which encodes a serine/threonine kinase, of unknown function.

Our data indicate that DNA methylation differences are apparent in MZ twins discordant for adolescent depression and that some of the disease-associated variation observed in buccal cell DNA is mirrored in adult brain tissue obtained from individuals with clinical depression.

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This work was supported by a grant awarded by the Psychiatric Research Trust (to TCE, JM, and ELD). The Genesis 12–19 Study collection waves 1–3 were funded by the William T. Grant Foundation, the University of London Central Research fund, and a Medical Research Council Training Fellowship and Career Development Award to TCE. Collection wave 4 was supported by the Economic and Social Research Council (Grant No. RES-000-22-2206) and the Institute of Social Psychiatry to AMG.

This study presents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.


Adolescent depression, depression, DNA methylation, epigenetic, genomics, monozygotic twins

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13 April 2014Accepted
6 May 2014Published Online
15 December 2014Published

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Date Deposited:

23 Jul 2014 16:25

Last Modified:

29 Apr 2020 16:00

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Yes, this version has been peer-reviewed.


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