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Journal of Zhejiang University. Science. B ; (12): 935-947, 2018.
Article Dans Anglais | WPRIM | ID: wpr-1010434

Résumé

OBJECTIVE@#As one of the most popular designs used in genetic research, family-based design has been well recognized for its advantages, such as robustness against population stratification and admixture. With vast amounts of genetic data collected from family-based studies, there is a great interest in studying the role of genetic markers from the aspect of risk prediction. This study aims to develop a new statistical approach for family-based risk prediction analysis with an improved prediction accuracy compared with existing methods based on family history.@*METHODS@#In this study, we propose an ensemble-based likelihood ratio (ELR) approach, Fam-ELR, for family-based genomic risk prediction. Fam-ELR incorporates a clustered receiver operating characteristic (ROC) curve method to consider correlations among family samples, and uses a computationally efficient tree-assembling procedure for variable selection and model building.@*RESULTS@#Through simulations, Fam-ELR shows its robustness in various underlying disease models and pedigree structures, and attains better performance than two existing family-based risk prediction methods. In a real-data application to a family-based genome-wide dataset of conduct disorder, Fam-ELR demonstrates its ability to integrate potential risk predictors and interactions into the model for improved accuracy, especially on a genome-wide level.@*CONCLUSIONS@#By comparing existing approaches, such as genetic risk-score approach, Fam-ELR has the capacity of incorporating genetic variants with small or moderate marginal effects and their interactions into an improved risk prediction model. Therefore, it is a robust and useful approach for high-dimensional family-based risk prediction, especially on complex disease with unknown or less known disease etiology.


Sujets)
Femelle , Humains , Mâle , Aire sous la courbe , Simulation numérique , Trouble de la conduite/physiopathologie , Santé de la famille , Marqueurs génétiques , Prédisposition génétique à une maladie , Variation génétique , Génome humain , Étude d'association pangénomique , Génomique , Fonctions de vraisemblance , Modèles génétiques , Odds ratio , Pedigree , Courbe ROC , Reproductibilité des résultats , Facteurs de risque
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