Establishment Of A Polygenic Risk Prediction Model For Narcolepsy In Han Chinese

In recent years,more and more common variants were identified using genome-wide association study,and there was great interest in incorporating the findings into screening individuals at high risk of disease.The purpose of this study was to discover susceptibility variants for further study by imputation and establish a polygenic risk prediction model among Han Chinese population and evaluate its discrimination ability for narcolepsy.In the present study,we performed the genome-wide association study including 1189 narcolepsy patients and 1997 controls,and established the two train sets and one test set.We have revealed 9 susceptibility variants which was associated with narcolepsy in each train set.Then we included these susceptibility variants in the risk prediction model.Besides,another 9 SNPs which were associated with narcolepsy in the previous genome-wide association study were involved in the risk prediction model.Therefore,we established a genetic risk prediction model by weighting the polygene risk scores of 18 loci with best discrimination power(ALL-SNP model,AUC: 0.826).We indicated the risk of narcolepsy among individual in the top quartile of polygenic risk scores was significantly higher than those in the lowest quartile for polygenic risk scores under ALL-SNP model(OR=27.8,P<0.0001).In addition,we also divided these 18 loci into two parts to construct a model(HLA model,AUC: 0.806;NO-HLA model,AUC: 0.705)and found two susceptibility loci which located in the HLA region(rs9271117 and rs7744020).These two susceptibility variants made great contribution to predicting the risk of narcolepsy.We also selected 10 SNPs from a genome-wide association study of European populations to construct a risk prediction model,which was inferior to the ALL-SNP model in the ability of prediction(AUC: 0.705).In the end,our results showed that the predictive model,established by these 18 sites,had the potential to screen high-risk groups of narcolepsy.