Genetics as a clinical tool in depression: are we there yet?

Despite initial obstacles, large-scale genome-wide association studies (GWAS) of unipolar depression, such as those conducted by the Psychiatric Genomics Consortium, have identified the location of many specific risk variants involved in the aetiology of the disorder. While such work continues and sample sizes grow, some researchers are turning their attention to whether genetics can be applied on a specific and translational level. Population-based cohorts provide real-world data on individuals affected by depression. These data offer a valuable opportunity to assess the utility of genetic information, including polygenic scores (PGSs) and copy number variants (CNVs), as clinical tools for important objectives, such as predicting disease course, identifying individuals who are likely or unlikely to respond to treatment, and understanding comorbid psychiatric, neurodevelopmental, and physical illnesses. In our symposium, four speakers will present their work investigating whether genetic measures offer promise for translational research in depression. Dr. Musliner will present the results of prediction models for progression to bipolar disorder and schizophrenia in patients with early-onset depression in the iPSYCH2015 sample. These models assess whether including PGSs improves our ability to predict which patients will progress onto a more severe psychiatric illness. Dr. Mundy will present research into PGSs as predictors of post-treatment functioning in patients with unipolar depression. By combining the iPSYCH2015 clinical sample with a genetically-informed design, Dr. Mundy investigates a) which genetic risk factors are associated with specific trajectories in unipolar depression, and b) whether previously identified sociodemographic and clinical risk factors, such as gender, socioeconomic status, and symptom severity, are associated with outcomes in depression independently from individual genetic risk. Dr. Shakeshaft will present research from the Norwegian Mother, Father, and Baby Cohort study into causal links between chronic physical illnesses in childhood, such as diabetes, asthma, eczema and epilepsy, and early-onset depression. In addition, she will present work examining whether there are causal associations using two-sample bidirectional Mendelian Randomisation in additional cohorts. Dr. Dennison will present work investigating the role of neurodevelopmental disorder-associated CNVs (NDD CNVs) in early-onset depression. She will present findings across multiple population cohorts examining whether NDD CNVs are enriched in individuals with depression onset prior to age 15, and the phenotypic manifestation of early-onset depression and NDD CNVs in children and young people. Our symposium will comment on whether we are “there yet” in terms of leveraging genetic information to elucidate and predict the real experiences of people with depression, what we have learnt thus far from population-level data, and the challenges that lie ahead.