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Phenome-wide analysis of genome-wide polygenic scores
E Krapohl1, J Euesden1, D Zabaneh1
1MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Molecular Psychiatry
|August 26, 2015
Summary
Genome-wide polygenic scores (GPS) can predict some adolescent behaviors. Cognitive GPS showed stronger prediction for educational achievement and behavior problems than psychiatric GPS in UK teens.
Area of Science:
- Behavioral genetics
- Psychiatric genetics
- Quantitative genetics
Background:
- Genome-wide polygenic scores (GPS) aggregate DNA variants from GWAS to predict individual traits.
- Investigating GPS associations with the behavioral phenome is crucial for understanding genetic influences on behavior.
- Current GPS derived from adult GWAS may have limitations when applied to adolescent development.
Purpose of the Study:
- To systematically investigate associations between GPS and a wide range of behavioral traits in adolescents.
- To compare the predictive power of cognitive GPS versus psychiatric GPS in a UK-representative adolescent sample.
- To explore the utility of GPS for stratifying individuals and identifying research opportunities.
Main Methods:
- Created 13 GPS from large GWAS for psychiatric and cognitive traits.
- Analyzed associations between GPS and 50 behavioral traits (psychopathology, personality, cognition, education) in 3152 adolescents.
- Examined phenome-wide association profiles across the full GPS distribution and at the extremes.
Main Results:
- Cognitive GPS demonstrated stronger predictive power than psychiatric GPS in the adolescent sample.
- Education GPS explained variation in adolescent behavior problems (~0.6%) and educational achievement (~2%).
- Highest and lowest septiles of education GPS showed significant differences in math grades and behavior problems.
Conclusions:
- Cognitive GPS show potential for predicting certain behavioral outcomes in adolescents, though effect sizes are modest.
- GPS enable stratification of individuals, offering avenues for further research into genetic predispositions.
- Further research is needed to refine GPS utility for predicting genetic propensities earlier in development.
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