Genetic Markers for Optimizing Treatment for Schizophrenia

Abstract

This document provides methods and materials related to genetic markers for predicting response to a treatment for schizophrenia (SZ). For example, methods for using such genetic markers to select optimal treatments are provided.

What is claimed is: 
     
         1 . A method of predicting a human patient's likely response to a treatment for schizophrenia (SZ), the method comprising determining the identity of an allele of at least one polymorphism listed in Tables 1-20, wherein the presence of an allele associated with a known response indicates the patient's likely response to the treatment. 
     
     
         2 . A method of selecting a treatment for schizophrenia (SZ) for administration to a human patient, the method comprising:
 determining the identity in the subject of an allele of at least one polymorphism listed in Tables 1-20;   comparing the identity of the allele in the subject to a reference allele of the same polymorphism, wherein the reference allele is associated with a known response to a treatment; and   selecting a treatment if the allele in the patient is the same as a reference allele that is associated with a positive response to that treatment.   
     
     
         3 . The method of  claim 1  or  2 , wherein the treatment is administration of an antipsychotic medication, and the at least one polymorphism is selected from the markers listed in Tables 1-20. 
     
     
         4 . The method of  claim 3 , wherein the antipsychotic medication is olanzapine, and the at least one polymorphism is selected from the markers listed in Tables 1, 6, 11, and 16. 
     
     
         5 . The method of  claim 4 , wherein the at least one polymorphism is nucleotide 31 of a sequence selected from the group consisting of SEQ ID NO:2971, 2019, 684, 1109, 1336, 2256, 4414, 3296, 3298, 1853, 2390, 2813, 4603, 3746, 1309, 1588, 1197, 1717, and 248. 
     
     
         6 . The method of  claim 3 , wherein the antipsychotic medication is risperidone, and the at least one polymorphism is selected from the markers listed in Tables 2, 7, 12, and 17. 
     
     
         7 . The method of  claim 6 , wherein the at least one polymorphism is nucleotide 31 of a sequence selected from the group consisting of SEQ ID NO:27, 3878, 882, 882, 1439, 4213, 457, 2394, 1571, 4598, 559, 914, 4340, 1895, 22, 3078, 23, or 4573. 
     
     
         8 . The method of  claim 3 , wherein the antipsychotic medication is quetiapine, and the at least one polymorphism is selected from the markers listed in Tables 3, 8, 13, and 18. 
     
     
         9 . The method of  claim 8 , wherein the at least one polymorphism is nucleotide 31 of a sequence selected from the group consisting of SEQ ID NO:4571, 2383, 3737, 694, 795, 695, 2162, 574, 4414, 56, 1416, 1835, 3201, 2445, 1292, 1291, 745, 746, and 3528. 
     
     
         10 . The method of  claim 3 , wherein the antipsychotic medication is perphenazine, and the at least one polymorphism is selected from the markers listed in Tables 4, 9, 14, and 19. 
     
     
         11 . The method of  claim 10 , wherein the at least one polymorphism is nucleotide 31 of a sequence selected from the group consisting of SEQ ID NO:48, 3715, 2829, 3869, 2240, 4282 2409, 2634, 3312, 2797, 1665, 4250, 507, 3077, 3303, 1508, 307. 
     
     
         12 . The method of  claim 3 , wherein the antipsychotic medication is ziprasidone, and the at least one polymorphism is selected from the markers listed in Tables 5, 10, 15, and 20. 
     
     
         13 . The method of  claim 12 , wherein the at least one polymorphism is nucleotide 31 of a sequence selected from the group consisting of SEQ ID NO:3092, 3424, 62, 297, 2618, 1787 788, 1711, 4425, 2159, 3475, 1738, 2429, 2538, and 3589. 
     
     
         14 . The method of  claims 1  or  2 , wherein determining the identity of an allele comprises obtaining a sample comprising DNA from the subject, and determining identity of the nucleotide at the polymorphic site. 
     
     
         15 . The method of  claim 14 , wherein determining the identity of the nucleotide comprises contacting the sample with a probe specific for a selected allele of the polymorphism, and detecting the formation of complexes between the probe and the selected allele of the polymorphism, wherein the formation of complexes between the probe and the test marker indicates the presence of the selected allele in the sample. 
     
     
         16 . The method of  claim 14 , wherein determining the identity of an allele comprises determining the identity of a nucleotide at position 31 of one of SEQ ID NOs: 1-4617. 
     
     
         17 . The method of  claims 1  or  2 , further comprising selecting or excluding a subject for enrollment in a clinical trial based on the identity of the allele. 
     
     
         18 . The method of  claims 1  or  2 , further comprising stratifying a subject population for analysis of a clinical trial based on the identity of the allele in the subjects. 
     
     
         19 . The method of  claim 2 , further comprising administering the selected treatment to the subject. 
     
     
         20 . The method of  claims 1  or  2 , wherein the response is selected from the group consisting of a change in a PANNS score; length of time until a discontinuation of therapy; likelihood of discontinuing therapy due to lack of efficacy; and likelihood of discontinuing therapy due to a serious adverse event. 
     
     
         21 . The method of  claim 2 , wherein a positive response is a decrease in a PANSS score relative to baseline; a long time until discontinuation of therapy; a low likelihood of discontinuing therapy due to lack of efficacy; and a low likelihood of discontinuing therapy due to a serious adverse event. 
     
     
         22 . The method of  claims 1  or  2 , further comprising recording the identity of the allele in a tangible medium. 
     
     
         23 . The method of  claims 1  or  2 , wherein the tangible medium comprises a computer-readable disk, a solid state memory device, or an optical storage device.