The use of polygenic risk scores to identify phenotypes associated with genetic risk of bipolar disorder and depression: A systematic review.

Background: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples. Aims: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes. Methods: Following PRISMA guidelines, we searched EMBASE, Medline and PsycINFO (from August 2009 – 14th March 2016) and references of included studies. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate. Results: Twenty-five studies were included. Overall, both polygenic risk scores were associated with other psychiatric disorders (not the discovery sample disorder) such as depression, schizophrenia and bipolar disorder, greater symptom severity of depression, membership of a creative profession and greater educational attainment. Both depression and bipolar polygenic risk scores explained small amounts of variance in most phenotypes (< 2%). Limitations: Many studies did not report standardised effect sizes. This prevented us from conducting a meta-analysis. Conclusions: Polygenic risk scores for BD and MDD are associated with a range of phenotypes and outcomes. However, they only explain a small amount of the variation in these phenotypes. Larger discovery and adequately powered target samples are required to increase power of the PRS approach. This could elucidate how genetic risk for bipolar disorder and depression is manifest and contribute meaningfully to stratified medicine.