Microsatellite Markers of Schizophrenia

Abstract

The invention includes methods of determining if a subject is at risk for developing schizophrenia (SZ).

1 . A method of determining a human subject's risk of developing schizophrenia (SZ), the method comprising:
 obtaining a sample comprising DNA from the subject;   determining the identity of both alleles of rs1573726 in the sample;   comparing the identity of the rs1573726 alleles in the subject to the alleles of rs1573726 in:
 (i) a relative of the subject who is affected with SZ, and 
 (ii) a relative of the subject who is not affected with SZ, 
   wherein the presence of an allele at rs1573726 in the subject that is the same as an allele in the relative who is affected with SZ, and is not the same as the allele in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ.   
     
     
         2 . The method of  claim 1 , further comprising determining the identity of both alleles of one or more of rs135221, rs763126, rs848768, rs2269523, rs738615, rs738596, rs738598, rs138844, or rs135819 in the subject, thereby determining a subject haplotype, and comparing the subject haplotype to
 (i) a haplotype in a relative of the subject who is affected with SZ, and   (ii) a haplotype in a relative of the subject who is not affected with SZ,   wherein the presence of a haplotype in the subject that is the same as the haplotype in the relative who is affected with SZ, and is not the same as the haplotype in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ.   
     
     
         3 . The method of  claim 1 , further comprising:
 obtaining a sample comprising DNA from a relative of the subject who is affected with SZ, and determining the genotype of rs1573726 in the sample; and   obtaining a sample comprising DNA from a relative of the subject who is not affected with SZ, and determining the identity of both alleles of rs1573726 in the sample.   
     
     
         4 . The method of  claim 1 , wherein the relative is a parent or sibling. 
     
     
         5 . The method of  claim 1 , wherein determining the identity of both alleles comprises:
 obtaining a sample comprising DNA from the subject; and   determining the identity of both alleles at rs1573726 in the sample.   
     
     
         6 . The method of  claim 1 , wherein the sample is obtained from the subject by a health care provider. 
     
     
         7 . The method of  claim 1 , wherein the sample is provided by the subject without the assistance of a health care provider. 
     
     
         8 . The method of  claim 1 , further comprising determining the presence or absence of one or more additional markers associated with schizophrenia. 
     
     
         9 . The method of  claim 1 , wherein the subject is a patient having, or at risk of, schizophrenia. 
     
     
         10 . The method of  claim 1 , wherein the subject is suffering from early, intermediate or aggressive schizophrenia. 
     
     
         11 . The method of  claim 1 , wherein the subject has one or more risk factors associated with SZ. 
     
     
         12 . The method of  claim 11 , wherein the risk factors associated with SZ include one or more of: a relative afflicted with schizophrenia, a genetically based phenotypic trait associated with risk for SZ; deficits in working memory; and mixed-handedness, particularly in females. 
     
     
         13 . The method of  claim 12 , wherein the subject has one or more of a grandparent, parent, uncle or aunt, sibling, or child who has or had SZ. 
     
     
         14 . The method of  claim 12 , wherein the genetically based phenotypic is eye tracking dysfunction. 
     
     
         15 . The method of  claim 1 , wherein the subject is a child, fetus, or embryo, and one of the relatives of the subject has SZ. 
     
     
         16 . The method of  claim 1 , further comprising administering a treatment to a subject identified as being at increased risk for developing SZ. 
     
     
         17 . The method of  claim 16 , wherein the treatment is a pharmacological or psychosocial treatment for SZ. 
     
     
         18 . The method of  claim 1 , further comprising stratifying a subject population for a clinical trial based on the genotype of rs1573726. 
     
     
         19 . A method of selecting a human subject for inclusion or exclusion in a clinical trial, the method comprising:
 obtaining a sample comprising DNA from the subject;   determining the identity of both alleles of rs1573726 in the sample;   comparing the identity of the alleles at rs1573726 in the subject to the alleles of rs1573726 in:
 (i) a relative of the subject who is affected with SZ, and 
 (ii) a relative of the subject who is not affected with SZ, 
   wherein the presence of an rs1573726 allele in the subject that is the same as the allele in the relative who is affected with SZ, and is not the same as an allele in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ; and   including or excluding the subject if the genotype indicates that the subject has an increased risk of developing SZ.   
     
     
         20 . The method of  claim 19 , further comprising determining the identity of both alleles of one or more of rs135221, rs763126, rs848768, rs2269523, rs738615, rs738596, rs738598, rs138844, or rs135819, thereby providing a subject haplotype, and comparing the subject haplotype to:
 (i) a haplotype in a relative of the subject who is affected with SZ, and   (ii) a haplotype in a relative of the subject who is not affected with SZ,   wherein the presence of a haplotype in the subject that is the same as the haplotype in the relative who is affected with SZ, and is not the same as the haplotype in the relative who is not affected with SZ, indicates that the subject has an increased risk of developing SZ; and   including or excluding the subject if the haplotype indicates that the subject has an increased risk of developing SZ.   
     
     
         21 . The method of  claim 19 , wherein the clinical trial is of a treatment for SZ.