Epigenetic signature of glucocorticoid receptor is associated with the familial component of depression: A twin-based study

Abstract

Introduction

Despite the fact that depression has an estimated heritability around 40%, there is no definitive candidate gene contributing to its etiology. The lack of an identified genetic component for high-heritability disorders, like depression, gave rise to the concept of missing heritability. The epigenetics’ field has pushed forward new hypotheses to fill this gap since transgenerational inheritance of epigenetic patterns has been described both in animal models and, more recently, in humans. Depression is usually associated with an abnormal stress response and an altered hypothalamic-pituitary-adrenal axis, regulated by the glucocorticoid receptor (coded by NR3C1 gene). Therefore, NR3C1 has been widely investigated as a functional candidate gene involved in anxious-depressive spectrum disorders (ADSD) although a more comprehensive study of its methylation is further required (Palma-Gudiel et al., 2015).

Aims

To analyze NR3C1 promoter's methylation and to study its association with anxious-depressive spectrum disorders.

Methods

The sample consisted of 48 pairs of monozygotic twins, from the UB twin register, grouped as concordant, discordant and healthy pairs depending on whether both, one or none of the co-twins of each pair were affected by a lifetime ADSD, according to DSM-IV criteria (SCID). DNA methylation was assessed by bisulfite conversion and subsequent pyrosequencing.

Results

Hypermethylation at specific CpG sites, not previously reported, was detected in concordant twin pairs as compared with discordant and healthy groups (P = 0.03).

Conclusions

The epigenetic pattern newly described in NR3C1 gene may be contributing to the familial component of depression and thus could be putatively explained by transgenerational inheritance of epigenetic phenomena.

Disclosure of interest

The authors have not supplied their declaration of competing interest.