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Polygenic risk score as clinical utility in psychiatry: a clinical viewpoint

Abstract

Genome-wide association studies (GWASs) have detected many susceptible variants for common diseases, including psychiatric disorders. However, because of the small effect size of each variant, clinical utility that aims for risk prediction and/or diagnostic assistance based on the individual “variants” is difficult to use. Therefore, to improve the statistical power, polygenic risk score (PRS) has been established and applied in the GWAS as a robust analytic tool. Although PRS has potential predictive ability, because of its current “insufficient” discriminative power at the individual level for clinical use, it remains limited solely in the research area, specifically in the psychiatric field. For a better understanding of the PRS, in this review, we (1) introduce the clinical features of psychiatric disorders, (2) summarize the recent GWAS/PRS findings in the psychiatric disorders, (3) evaluate the problems of PRS, and (4) propose its possible utility to apply PRS into the psychiatric clinical setting.

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Acknowledgements

The authors thank Professor Yoichiro Kamatani (The University of Tokyo), Professor George Kirov (Cardiff University) for their thoughtful comments, and MARUZEN-YUSHODO Co., Ltd (https://kw.maruzen.co.jp/kousei-honyaku/) for the English language editing. This work was supported by the Strategic Research Program for Brain Sciences (SRPBS) from the Japan Agency for Medical Research and Development (AMED) under Grant number JP20dm0107097 (NI, MI, and TS); GRIFIN of P3GM from AMED under Grant numbers JP20km0405201 (TS and NI) and JP20km0405208 (MI); Health and Labor Sciences Research Grant under Grant number 20GC1017 (TK); JSPS Kakenhi Grant numbers JP25293253 (NI), JP16H05378 (NI), JP26293266 (MI), JP17H04251 (MI), and JP18K15497 (TS); and the Private University Research Branding Project from MEXT (NI).

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Correspondence to Masashi Ikeda.

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Ikeda, M., Saito, T., Kanazawa, T. et al. Polygenic risk score as clinical utility in psychiatry: a clinical viewpoint. J Hum Genet 66, 53–60 (2021). https://doi.org/10.1038/s10038-020-0814-y

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