Polygenic Risk Scores Do Not Explain Variation Associated With Genetic Risk for BD, MDD

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Higher polygenic risk scores for bipolar disorder were associated with post-traumatic stress disorder.
Higher polygenic risk scores for bipolar disorder were associated with post-traumatic stress disorder.

Polygenic risk scores for bipolar disorder (BD) and major depressive disorder (MDD) are associated with a range of phenotypes and outcomes, but they fail to explain more than a small amount of the variation in these phenotypes, according to a systematic review published in the Journal of Affective Disorders.

Sumit Mistry, PhD candidate, Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Wales, and colleagues searched EMBASE, Medline, and PsycINFO from August 2009 to March 14, 2016, as well as the references of included studies, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

The investigators included 25 studies that examined associations between the MDD and BD polygenic risk scores and a measurable phenotype. Higher MDD and BD polygenic risk scores were associated with increased risk for different psychopathologies. The researchers noted that the results of the review highlight that the polygenic risk scores for MDD and BD explain only a small proportion of the variance for all phenotypes: less than 2%. They argue that the variance explained will likely increase as discovery sample sizes increase, although this may be limited as the polygenic risk score does not capture rare single-nucleotide polymorphisms or copy number variant contribution to variance.

The investigators also contend that at the present time, the polygenic risk score approach is not useful for informing clinical practice or pharmacologic intervention. Furthermore, genetic risk for MDD and BD manifests in the adult population as a range of psychopathologies.

The study was limited by the limitations of the studies reviewed. The researchers used a narrative approach to summarizing the results, as most studies did not report standardized effect sizes, so it was not possible to conduct a meta-analysis.

Reference

Mistry S, Harrison JR, Smith DJ, Escott-Price V, Zammit S. The use of polygenic risk scores to identify phenotypes associated with genetic risk of bipolar disorder and depression: a systematic review. J Affect Disord. 2018;234:148-155.

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