Twin study designs as a tool to identify new candidate genes for depression: A systematic review of DNA methylation studies

• Published in: Neuroscience and biobehavioral reviews Vol. 112; pp. 345 - 352
• Main Authors: Palma-Gudiel, Helena, Córdova-Palomera, Aldo, Navarro, Víctor, Fañanás, Lourdes
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.05.2020
• Subjects: Depression; Depression - genetics; Depressive Disorder - genetics; DNA methylation; DNA Methylation - genetics; Epigenesis, Genetic - genetics; Epigenetics; Humans; Twin Studies as Topic; Twin study designs; Twin study designs; DNA methylation; Epigenetics; Depression
• ISSN: 0149-7634; 1873-7528; 1873-7528
• DOI: 10.1016/j.neubiorev.2020.02.017

•MZ twin studies enable the search for DNA methylation biomarkers of depression.•Genome-wide differential methylation probes are identified despite small sample sizes.•Depressed twins exhibit higher methylation variability than healthy co-twins.•Considering magnitude of methylation change helps in the detection of relevant hits.•Future studies should explore psychosocial stress to understand the role of methylation. Monozygotic (MZ) twin studies constitute a key resource for the dissection of environmental and biological risk factors for human complex disorders. Given that epigenetic differences accumulate throughout the lifespan, the assessment of MZ twin pairs discordant for depression offers a genetically informative design to explore DNA methylation while accounting for the typical confounders of the field, shared by co-twins of a pair. In this review, we systematically evaluate all twin studies published to date assessing DNA methylation in association with depressive phenotypes. However, difficulty to recruit large numbers of MZ twin pairs fails to provide enough sample size to develop genome-wide approaches. Alternatively, region and pathway analysis revealed an enrichment for nervous system related functions; likewise, evidence supports an accumulation of methylation variability in affected subjects when compared to their co-twins. Nevertheless, longitudinal studies incorporating known risk factors for depression such as childhood trauma are required for understanding the role that DNA methylation plays in the etiology of depression.