Variants of GRM7 as risk factor and response to antipsychotic therapy in schizophrenia

摘要

Genome-wide association study (GWAS) has determined the metabotropic glutamate receptor 7 (GRM7) gene aspotential locus for schizophrenia risk variants; However, the relationship between the GRM7 variants and the risk ofschizophrenia is still uncertain, and there are significant individual variations in response to the antipsychotic drugs. Inorder to identify susceptible gene and drug-response-related markers, 2413 subjects in our research were chosen fordetermining drug-response-related markers in schizophrenia. The rs1516569 variant (OR = 0.95, P 3.47 × 10?4) was asignificant risk factor, and a single-nucleotide polymorphism of GRM7 gene- rs9883258 (OR = 0.84, P = 2.18 × 10?3) hasbeen determined as potential biomarkers for therapeutic responses of seven commonly used antipsychotic drugs(aripiprazole, haloperidol, olanzapine, perphenazine, quetiapine, risperidone and ziprasidone) in Chinese Hanpopulation; Significant associations with treatment response for several single-nucleotide polymorphisms in everyantipsychotic drugs, such as rs779746 (OR = 1.39, P = 0.03), rs480409 (OR = 0.73, P = 0.04), rs78137319 (OR = 3.09, P =0.04), rs1154370 (OR = 1.51, P = 0.006) have been identified in our study. Hence our research elucidates that GRM7variants play the critical role of predicting the risk of schizophrenia and antipsychotic effect of seven common drugs.