Genome-wide methylomic analysis of monozygotic twins discordant for adolescent depression.
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
['Dempster|Emma L|EL|', 'Wong|Chloe C Y|CC|', 'Lester|Kathryn J|KJ|', 'Burrage|Joe|J|', 'Gregory|Alice M|AM|', 'Mill|Jonathan|J|', 'Eley|Thalia C|TC|']
D000293:Adolescent D002531:Cerebellum D018899:CpG Islands D019175:DNA Methylation D003863:Depression D005260:Female D016678:Genome D015894:Genome, Human D006801:Humans D008297:Male D011180:Postmortem Changes D011795:Surveys and Questionnaires D014430:Twins, Monozygotic
monozygotic twins Adolescent depression depression epigenetic DNA methylation genomics