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Abstract

Genomewide association studies (GWASs) across psychiatric phenotypes have shown that common genetic variants generally confer risk with small effect sizes (odds ratio < 1.1) that additively contribute to polygenic risk. Summary statistics derived from large discovery GWASs can be used to generate polygenic risk scores (PRS) in independent, target data sets to examine correlates of polygenic disorder liability (e.g., does genetic liability to schizophrenia predict cognition?). The intuitive appeal and generalizability of PRS have led to their widespread use and new insights into mechanisms of polygenic liability. However, when currently applied across traits they account for small amounts of variance (<3%), are relatively uninformative for clinical treatment, and, in isolation, provide no insight into molecular mechanisms. Larger GWASs are needed to increase the precision of PRS, and novel approaches integrating various data sources (e.g., multitrait analysis of GWASs) may improve the utility of current PRS.

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2018-05-07
2024-04-18
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