Methylation of 3 Genetic Sites Linked to Depressive Symptoms

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All of the findings lead toward axon guidance as the common disrupted pathway in depression.
All of the findings lead toward axon guidance as the common disrupted pathway in depression.

The methylation of 3 DNA sites is associated with increased depressive symptoms, according to study results published in JAMA Psychiatry.

These results warrant further studies to determine whether the methylation of these sites can be used as biomarkers for depression and to evaluate the role they play in the pathophysiology of depression.

The researchers performed a cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart Aging and Research in Genomic Epidemiology (CHARGE) Consortium. The EWAS included 7948 participants of European origin from 9 population-based cohorts. The researchers replicated the top epigenetic sites with 3308 participants of African-American and European origin from 2 population-based cohorts.

The study included participants who were assessed for both depressive symptoms and whole-blood DNA methylation. The researchers assayed whole-blood DNA methylation levels using Illumina-Infinium Human Methylation 450K BeadChip and assessed depressive symptoms using a questionnaire.

The EWAS found methylation of cg04987734 (P =1.57×10−08; n=11,256; CDC42BPB gene), cg12325605 (P =5.24×10−09; n=11,256; ARHGEF3 gene), and an intergenic CpG site cg14023999 (P =5.99×10−08; n=11,256; chromosome 15q26.1) were significantly associated with increased depression symptoms.

The researchers also found that the predicted expression of the CDC42BPB gene in the basal ganglia of the brain (effect, 0.14; P =2.7×10−03) and of ARHGEF3 in fibroblasts (effect, −0.48; P =9.8×10−04) were associated with major depression.

All 3 sites associated with depressive symptoms were either genes or had associations with genes expressed in the brain and converged to the axon guidance pathway, suggesting that axon guidance is the common disrupted pathway in depression.

“This study suggests that robust DNA methylation signatures of depression are identifiable in blood and that these signatures may be similar across various races/ethnicities,” the researchers wrote.

Reference

Jovanova OS, Nedeljkovic I, Derek S, et al. DNA methylation signatures of depressive symptoms in middle-aged and elderly persons: meta-analysis of multiethnic epigenome-wide studies [published online July 11, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.1725

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