Polygenic Risk Scores! What are they?

Image A: colourful corals

Week 4 - What are polygenic (risk) scores and how can they be used in mental health research?

A polygenic risk score (PRS) is a number that explains your disease risk based on your genes. The scores are calculated using many single nucleotide polymorphisms (SNPs) at the same time. These numbers are based on variation in multiple genetic loci and their associated weights. Polygenic risk scores have become the standard for quantifying polygenic risk in mental health research, particularly in genetic wide association studies (GWAS).

PRS can predict various phenotypes, such as neurodevelopmental outcomes (Riglin et al., 2017) and creativity in individuals with disorders (Power et al., 2015). However, PRS are limited in their ability to predict disorder and disease risk (Barr et al., 2020). This means they can slightly improve risk prediction for common diseases but also have modest benefits. This modest effect is shown in Power et al.'s (2015) research. I actually presented the aims and results of this research paper with two other people in front of my classmates for a module assignment back in my final year of university! Only a small amount of variance is explained by PRS for corresponding disorders; 5.5% for schizophrenia, and 1.2% for bipolar disorder. The present study also found an association between PRS for corresponding diseases, and creativity. Scores for schizophrenia and bipolar disorder only explained a maximum of 0.24% and 0.26% of the variance for creativity, respectively. Another limitation is that much of an individual's disease risk is determined by factors that PRS cannot measure, such as environmental or non-genetic factors. Further research must continue to challenge the validity of PRS (Janssens, 2019).

One research implication of the findings is that we may better understand the minds of individuals with schizophrenia and bipolar disorder, and how creativity thrives in circumstances that would otherwise be considered as negative. Society believes that polygenic traits that affect the risk of schizophrenia and bipolar disorder are detrimental to the individuals who carry them, but such traits are really a positive thing especially when it comes to allowing individuals to express their creativity.

References

Barr, P. B., Ksinan, A., Su, J., Johnson, E. C., Meyers, J. L., Wetherill, L., ... & Dick, D. M. (2020). Using polygenic scores for identifying individuals at increased risk of substance use disorders in clinical and population samples. Translational Psychiatry, 10(1), 196.

Janssens, A. C. J. (2019). Validity of polygenic risk scores: are we measuring what we think we are?. Human molecular genetics, 28(R2), R143-R150.

Power, R. A., Steinberg, S., Bjornsdottir, G., Rietveld, C. A., Abdellaoui, A., Nivard, M. M., ... & Stefansson, K. (2015). Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nature neuroscience, 18(7), 953-955.

Riglin, L., Collishaw, S., Richards, A., Thapar, A. K., Maughan, B., O'Donovan, M. C., & Thapar, A. (2017). Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: a population-based cohort study. The Lancet Psychiatry, 4(1), 57-62.

I had a lot of fun researching and writing for this blog post, considering I had to do an entire presentation on one of the referenced papers I really got into the nitty gritty of this assignment. Hope you enjoyed reading this one, I'll see you for the next one!

Signing off,

burnt toast, sweet tea;