The use of Polygenic Risk Scores to Inform Aetiology of Mood and Psychotic Disorders

Abstract

Introduction

Polygenic risk scores (PRS) incorporate many small genetic markers that are associated with conditions. This technique was first used to investigate mental illnesses in 2009. Since then, it has been widely used.

Objectives

We wanted to explore how PRS have been used to the study the aetiology of psychosis, schizophrenia, bipolar disorder and depression.

Aims

We aimed to conduct a systematic review, identifying studies that have examined associations between PRS for bipolar disorder, schizophrenia/psychosis and depression and psychopathology-related outcome measures.

Methods

We searched EMBASE, Medline and PsychInfo from 06/08/2009 to 14/03/2016. We hand-searched the reference lists of related papers.

Results

After removing duplicates, the search yielded 1043 publications. When irrelevant articles were excluded, 33 articles remained. We found 24 studies using schizophrenia PRS, three using bipolar PRS and nine using depression PRS. Many studies successfully used PRS to predict case/control status. Some studies showed associations between PRS and diagnostic sub-categories. A range of clinical phenotypes and symptoms has been explored. For example, specific PRS are associated with cognitive performance in schizophrenia, psychotic symptoms in bipolar disorder, and frequency of episodes of depression. PRS have also demonstrated genetic overlap between mental illnesses. It was difficult to assess the quality of some studies as not all reported sufficient methodological detail.

Conclusions

PRS have enabled us to explore the polygenic architecture of mental illness and demonstrate a genetic basis for some observed features. However, they have yet to give insights into the biology, which underpin mental illnesses.

Disclosure of interest

The authors have not supplied their declaration of competing interest.