Genetic Markers for Assessing Risk of Developing Bipolar Disorder

Abstract

This document provides methods and materials related to genetic markers of Bipolar Disorder (BD) and Schizophrenia (SZ). For example, methods for using such genetic markers to assess risk of developing BD and/or SZ are provided, as are methods for making a differential diagnosis between BD and SZ.

1 . A method of determining relative risk of developing bipolar disorder (BD) versus schizophrenia (SZ) in a human subject, the method comprising:
 obtaining a sample comprising genomic DNA from the subject;   determining the identity of an allele of a single nucleotide polymorphism (SNP) at rs2060147 in the Disks Large Homolog 2 (DLG2) gene in the sample; and   identifying a subject who has a guanine (G) allele at rs2060147 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147.   
     
     
         2 . The method of  claim 1 , wherein determining the identity of an allele at rs2060147 comprises: contacting the sample with a probe specific for an allele at rs2060147;
 and detecting the formation of complexes between the probe and the allele,   wherein the formation of complexes between the probe and the allele indicates the presence of the allele in the sample.   
     
     
         3 . The method of  claim 1 , wherein determining the identity of an allele at rs2060147 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2409. 
     
     
         4 . The method of  claim 1 , wherein the subject is a patient having or suspected of having BD or SZ. 
     
     
         5 . The method of  claim 1 , wherein the subject has one or more risk factors associated with BD or SZ. 
     
     
         6 . The method of  claim 5 , wherein the risk factors associated with BD or SZ include one or more of: a relative afflicted with BD or SZ; and a genetically based phenotypic trait associated with risk for BD or SZ. 
     
     
         7 . The method of  claim 1 , wherein the subject has exhibited or exhibits symptoms of psychosis. 
     
     
         8 . The method  claim 7 , wherein the psychosis is associated with BD or SZ. 
     
     
         9 . The method of  claim 1 , further comprising selecting or excluding a subject for enrollment in a clinical trial based on the identity of the allele. 
     
     
         10 . The method of  claim 1 , further comprising stratifying a subject population for analysis of a clinical trial based on the identity of the allele in the subjects. 
     
     
         11 . The method of  claim 1 , further comprising confirming a diagnosis of SZ or BD using psychometric instruments. 
     
     
         12 . The method of  claim 1 , further comprising selecting a treatment for BD if the allele in the subject indicates that the subject has an increased risk of developing BD, or selecting a treatment for SZ if an allele in the subject indicates that the subject has an increased risk of developing SZ. 
     
     
         13 . The method of  claim 12 , further comprising administering the selected treatment to the subject. 
     
     
         14 . The method of  claim 12 , wherein the treatment is psychotherapy. 
     
     
         15 . The method of  claim 1 , further comprising recording the identity of the allele in a tangible medium. 
     
     
         16 . The method of  claim 15 , wherein the tangible medium comprises a computer-readable disk, a solid state memory device, or an optical storage device. 
     
     
         17 . The method of  claim 1 , comprising determining the identity of both alleles at rs2060147 in the sample, and identifying a subject who has two G alleles at rs2060147 as having an increased risk of developing BD instead of SZ, as compared to a subject having one G allele at rs2060147 or lacking a G allele at rs2060147. 
     
     
         18 . The method of  claim 1 , further comprising determining the identity of an additional SNP in the DLG2 gene in the sample. 
     
     
         19 . The method of  claim 18 , wherein the additional SNP in the DLG2 gene is selected from the group consisting of: rs1367980, rs4480567, rs983590, rs11233711, rs12225388, rs10898148, rs12222455, rs10898152, rs7950988, and rs1945309. 
     
     
         20 . The method of  claim 19 , further comprising one or more of:
 identifying a subject who has a G allele at rs2060147 and a G allele at rs1367980 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking a G allele at rs1367980;   identifying a subject who has a G allele at rs2060147 and a cytosine (C) allele at rs4480567 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking a C at rs4480567;   identifying a subject who has a G allele at rs2060147 and a thymine (T) allele at rs983590 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking a T at rs983590;   identifying a subject who has a G allele at rs2060147 and a T allele at rs11233711 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking a T at rs11233711;   identifying a subject who has a G allele at rs2060147 and an adenine (A) allele at rs12225388 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking an A allele at rs12225388;   identifying a subject who has a G allele at rs2060147 and an A allele at rs10898148 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking an A allele at rs10898148;   identifying a subject who has a G allele at rs2060147 and an A allele at rs12222455 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking an A allele at rs12222455;   identifying a subject who has a G allele at rs2060147 and a C allele at rs10898152 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking a C allele at rs10898152;   identifying a subject who has a G allele at rs2060147 and a T allele at rs7950988 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking a I allele at rs7950988; and   identifying a subject who has a G allele at rs2060147 and an A allele at rs1945309 as having an increased risk of developing BD instead of SZ, as compared to a subject lacking a G allele at rs2060147 and lacking an A allele at rs1945309.   
     
     
         21 . The method of  claim 19 , wherein:
 determining the identity of an allele at rs1367980 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2407;   determining the identity of an allele at rs4480567 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2408;   determining the identity of an allele at rs983590 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2410;   determining the identity of an allele at rs11233711 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2411;   determining the identity of an allele at rs12225388 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2412;   determining the identity of an allele at rs10898148 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2413;   determining the identity of an allele at rs12222455 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2414;   determining the identity of an allele at rs10898152 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2415;   determining the identity of an allele at rs7950988 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2416; or   determining the identity of an allele at rs1945309 comprises determining the identity of the nucleotide at position 31 of SEQ ID NO: 2417.