Phenome-wide analysis of genome-wide polygenic scores

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Krapohl, E; Euesden, J; Zabaneh, D; Pingault, J-B; Rimfeld, K; Von Stumm, Sophie; Dale, P S; Breen, G; O'Reilly, P F and Plomin, R. 2016. Phenome-wide analysis of genome-wide polygenic scores. Molecular Psychiatry, 21(9), pp. 1188-1193. ISSN 1359-4184 [Article]

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Official URL: https://www.nature.com/articles/mp2015126

Abstract or Description

Genome-wide polygenic scores (GPS), which aggregate the effects of thousands of DNA variants from genome-wide association studies (GWAS), have the potential to make genetic predictions for individuals. We conducted a systematic investigation of associations between GPS and many behavioral traits, the behavioral phenome. For 3152 unrelated 16-year-old individuals representative of the United Kingdom, we created 13 GPS from the largest GWAS for psychiatric disorders (for example, schizophrenia, depression and dementia) and cognitive traits (for example, intelligence, educational attainment and intracranial volume). The behavioral phenome included 50 traits from the domains of psychopathology, personality, cognitive abilities and educational achievement. We examined phenome-wide profiles of associations for the entire distribution of each GPS and for the extremes of the GPS distributions. The cognitive GPS yielded stronger predictive power than the psychiatric GPS in our UK-representative sample of adolescents. For example, education GPS explained variation in adolescents’ behavior problems (~0.6%) and in educational achievement (~2%) but psychiatric GPS were associated with neither. Despite the modest effect sizes of current GPS, quantile analyses illustrate the ability to stratify individuals by GPS and opportunities for research. For example, the highest and lowest septiles for the education GPS yielded a 0.5 s.d. difference in mean math grade and a 0.25 s.d. difference in mean behavior problems. We discuss the usefulness and limitations of GPS based on adult GWAS to predict genetic propensities earlier in development.

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Article

Identification Number (DOI):

https://doi.org/10.1038/mp.2015.126

Additional Information:

We gratefully acknowledge the ongoing contribution of the participants in the Twins Early Development Study (TEDS) and their families. TEDS is supported by a program grant to RP from the UK Medical Research Council (G0901245; and previously G0500079), with additional support from the US National Institutes of Health (HD044454; HD059215). EK is supported by a Medical Research Council studentship. RP is supported by a Medical Research Council Research Professorship award (G19/2) and a European Research Council Advanced Investigator award (295366). GB was funded in part by the National Institute for Health Research Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London.