Approved Research

Calculation of a polygenic score for circadian depression, its association with clinical variables, and predictive value for mood disorders.

Lay summary

Depression affects more than 300 million people worldwide and is amongst the highest-ranked cause of disability. The cause and biological processes underlying depression remain unclear, while traditional treatments are unsuccessful for many.

We hypothesize that a dysregulation of the circadian system, a biological network regulating the timing of all physiology and behavior, plays a causative role on the onset, course, and treatment of a subgroup of depression, referred to as "circadian depression". Individuals in this subtype expressed features such as delayed sleep-wake phase, hypersomnia, non-restorative sleep, low energy, prolonged fatigue, weight gain and somatic complaints.

In this project, we aim to construct a circadian depression phenotype using variables available in the UK Biobank, and to calculate a GWAS for this phenotype to identify genes involved in this pathophysiological pathway. Next, we will calculate a polygenic score of circadian depression to investigate associations between genetic vulnerability for circadian depression and key clinical variables, such as poor response or adverse effect to traditional antidepressant treatments, atypical features, such as weight gain, increased appetite, subjective and objective measures of activity, and chronotype. We will also test whether genetic vulnerability contributes to predicting the onset of mood disorders in young people.