GENETIC MARKERS FOR SCHIZOPHRENIA AND BIPOLAR DISORDER
First Claim
Patent Images
1. A method of determining a human subject'"'"'s risk of developing schizophrenia (SZ) or bipolar disorder (BD), the method comprising:
- obtaining a test haplotype for the subject by determining the genotype for one or more test markers in the HPCAL1 gene between and including SNPs rs4668676 (SEQ ID NO;
1) and rs12692407 (SEQ ID NO;
11), or in the SV2C gene between and including SNPs rs889189 (SEQ ID NO;
12) and rs31244 (SEQ ID NO;
19), wherein the one or more test markers are selected from the group consisting of;
rs4668676 (SEQ ID NO;
1) or a marker in linkage disequilibrium therewith;
rs6714483 (SEQ ID NO;
2) or a marker in linkage disequilibrium therewith;
rs17882379 (SEQ ID NO;
3) or a marker in linkage disequilibrium therewith;
rs6755271 (SEQ ID NO;
4) or a marker in linkage disequilibrium therewith;
rs887973 (SEQ ID NO;
5) or a marker in linkage disequilibrium therewith;
rs11893459 (SEQ ID NO;
6) or a marker in linkage disequilibrium therewith;
rs2270299 (SEQ ID NO;
7) or a marker in linkage disequilibrium therewith;
rs1808315 (SEQ ID NO;
8) or a marker in linkage disequilibrium therewith;
rs11694643 (SEQ ID NO;
9) or a marker in linkage disequilibrium therewith;
rs3732120 (SEQ ID NO;
10) or a marker in linkage disequilibrium therewith;
rs12692407 (SEQ ID NO;
10) or a marker in linkage disequilibrium therewith;
rs889189 ((SEQ ID NO;
11) or a marker in linkage disequilibrium therewith;
rs736005 (SEQ ID NO;
12) or a marker in linkage disequilibrium therewith;
rs6453211 (SEQ ID NO;
13) or a marker in linkage disequilibrium therewith;
rs4704298 (SEQ ID NO;
14) or a marker in linkage disequilibrium therewith;
rs1501926 (SEQ ID NO;
15) or a marker in linkage disequilibrium therewith;
rs11960621 (SEQ ID NO;
17) or a marker in linkage disequilibrium therewith;
rs2270927 (SEQ ID NO;
18) or a marker in linkage disequilibrium therewith; and
rs31244 (SEQ ID NO;
19) or a marker in linkage disequilibrium therewith;
wherein the test haplotype indicates the subject'"'"'s risk of developing SZ or BD.
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Accused Products
Abstract
The invention provides haplotypes and SNPs of the HPCAL1 and SV2C genes which predict the risk for developing schizophrenia or bipolar disorder and predict which patients are likely to respond to a given treatment or are more likely to experience negative side effects.
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Citations
32 Claims
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1. A method of determining a human subject'"'"'s risk of developing schizophrenia (SZ) or bipolar disorder (BD), the method comprising:
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obtaining a test haplotype for the subject by determining the genotype for one or more test markers in the HPCAL1 gene between and including SNPs rs4668676 (SEQ ID NO;
1) and rs12692407 (SEQ ID NO;
11), or in the SV2C gene between and including SNPs rs889189 (SEQ ID NO;
12) and rs31244 (SEQ ID NO;
19), wherein the one or more test markers are selected from the group consisting of;rs4668676 (SEQ ID NO;
1) or a marker in linkage disequilibrium therewith;rs6714483 (SEQ ID NO;
2) or a marker in linkage disequilibrium therewith;rs17882379 (SEQ ID NO;
3) or a marker in linkage disequilibrium therewith;rs6755271 (SEQ ID NO;
4) or a marker in linkage disequilibrium therewith;rs887973 (SEQ ID NO;
5) or a marker in linkage disequilibrium therewith;rs11893459 (SEQ ID NO;
6) or a marker in linkage disequilibrium therewith;rs2270299 (SEQ ID NO;
7) or a marker in linkage disequilibrium therewith;rs1808315 (SEQ ID NO;
8) or a marker in linkage disequilibrium therewith;rs11694643 (SEQ ID NO;
9) or a marker in linkage disequilibrium therewith;rs3732120 (SEQ ID NO;
10) or a marker in linkage disequilibrium therewith;rs12692407 (SEQ ID NO;
10) or a marker in linkage disequilibrium therewith;rs889189 ((SEQ ID NO;
11) or a marker in linkage disequilibrium therewith;rs736005 (SEQ ID NO;
12) or a marker in linkage disequilibrium therewith;rs6453211 (SEQ ID NO;
13) or a marker in linkage disequilibrium therewith;rs4704298 (SEQ ID NO;
14) or a marker in linkage disequilibrium therewith;rs1501926 (SEQ ID NO;
15) or a marker in linkage disequilibrium therewith;rs11960621 (SEQ ID NO;
17) or a marker in linkage disequilibrium therewith;rs2270927 (SEQ ID NO;
18) or a marker in linkage disequilibrium therewith; andrs31244 (SEQ ID NO;
19) or a marker in linkage disequilibrium therewith;wherein the test haplotype indicates the subject'"'"'s risk of developing SZ or BD. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 31, 32)
sharing of a haplotype between the test haplotype and the reference haplotype from the relative who has SZ, SD, SPD or BD, and lack of sharing of a haplotype of a haplotype between the test haplotype and the reference haplotype from the unaffected relative, is indicative of an increased likelihood that the subject will develop broadly defined SZ or BD.
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8. The method of claim 1, further comprising determining the genotype of one or more additional markers listed in Table A, or one or more test markers that are in linkage disequilibrium with a marker listed in Table A.
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9. The method of claim 1, wherein the subject is a patient having or suspected of having SZ or BD.
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10. The method of claim 1, wherein the subject has one or more risk factors associated with SZ or BD.
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11. The method of claim 10, wherein the risk factors associated with SZ or BD include one or more of:
- a relative afflicted with SZ, SPD, SD or BD and a genetically based phenotypic trait associated with risk for SZ, SPD, SD or BD.
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12. The method of claim 1, wherein the subject is a child, fetus, or embryo.
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13. The method of claim 1, further comprising administering a pharmacological treatment to a subject identified as being at altered risk for developing SZ or BD.
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14. The method of claim 1, wherein the test haplotype further provides information that differentiates patients that are more likely to respond to a treatment from those who are less likely to respond, or patients that are more likely to experience negative side effects from those less likely to experience negative side effects.
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15. The method of claim 1, further comprising selecting or excluding a subject for enrollment in a clinical trial based on the test haplotype.
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16. The method of claim 1, further comprising stratifying a subject population for analysis of a clinical trial based on the test haplotypes in the subjects.
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17. The method of claim 1, further comprising confirming a diagnosis of SZ or BD using a psychometric instrument.
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18. The method of claim 1, further comprising stratifying patients into biologically similar groups based on test haplotypes in order to determine a differential diagnosis.
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31. The method of claim 1, wherein obtaining a test haplotype comprises obtaining a sample comprising genomic DNA of the subject, and determining the identity of the alleles at the test markers.
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32. The method of claim 1, wherein obtaining a test haplotype comprises constructing test haplotypes from previous genotyping results, wherein the previous genotyping results include at least one test marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A.
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19. An array comprising a substrate having a plurality of addressable areas, wherein one or more of the addressable areas comprises a probe that can be used to detect two or more polymorphisms listed in Table A or Table B.
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20. A method of predicting an effect of a haplotype on the outcome of a treatment for schizophrenia (SZ), schizotypal personality disorder (SPD), schizoaffective disorder (SD), or bipolar disorder (BD), the method comprising:
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obtaining a test haplotype for the subject by determining the genotype for one or more test markers in the HPCAL1 gene between and including SNPs rs4668676 (SEQ ID NO;
1) and rs12692407 (SEQ ID NO;
11), or in the SV2C gene between and including SNPs rs889189 (SEQ ID NO;
12) and rs31244 (SEQ ID NO;
19), wherein the one or more test markers are selected from the group consisting of;rs4668676 (SEQ ID NO;
1) or a marker in linkage disequilibrium therewith;rs6714483 (SEQ ID NO;
2) or a marker in linkage disequilibrium therewith;rs17882379 (SEQ ID NO;
3) or a marker in linkage disequilibrium therewith;rs6755271 (SEQ ID NO;
4) or a marker in linkage disequilibrium therewith;rs887973 (SEQ ID NO;
5) or a marker in linkage disequilibrium therewith;rs11893459 (SEQ ID NO;
6) or a marker in linkage disequilibrium therewith;rs2270299 (SEQ ID NO;
7) or a marker in linkage disequilibrium therewith;rs1808315 (SEQ ID NO;
8) or a marker in linkage disequilibrium therewith;rs11694643 (SEQ ID NO;
9) or a marker in linkage disequilibrium therewith;rs3732120 (SEQ ID NO;
10) or a marker in linkage disequilibrium therewith;rs12692407 (SEQ ID NO;
10) or a marker in linkage disequilibrium therewith;rs889189 ((SEQ ID NO;
11) or a marker in linkage disequilibrium therewith;rs736005 (SEQ ID NO;
12) or a marker in linkage disequilibrium therewith;rs6453211 (SEQ ID NO;
13) or a marker in linkage disequilibrium therewith;rs4704298 (SEQ ID NO;
14) or a marker in linkage disequilibrium therewith;rs1501926 (SEQ ID NO;
15) or a marker in linkage disequilibrium therewith;rs11960621 (SEQ ID NO;
17) or a marker in linkage disequilibrium therewith;rs2270927 (SEQ ID NO;
18) or a marker in linkage disequilibrium therewith; andrs31244 (SEQ ID NO;
19) or a marker in linkage disequilibrium therewith;wherein the test haplotype indicates the subject'"'"'s likely response to the treatment.
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21. A method of selecting a subject for inclusion in a clinical trial, the method comprising:
- obtaining a haplotype for the subject comprising at least one marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
determining whether the haplotype is associated with altered response to a clinical treatment; and
including the subject if the haplotype indicates that the subject has altered response to the clinical treatment in question. - View Dependent Claims (22)
- obtaining a haplotype for the subject comprising at least one marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
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23. A method of selecting a subject for administration of a treatment for schizophrenia (SZ), schizotypal personality disorder (SPD), schizoaffective disorder (SD), or bipolar disorder (BD), the method comprising:
- obtaining a haplotype for the subject, wherein the haplotype comprises at least one marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
determining whether the haplotype is associated with an altered response profile for a clinical treatment; and
selecting the subject if the haplotype indicates that the subject is more likely to have an improved response profile to the clinical treatment in question.
- obtaining a haplotype for the subject, wherein the haplotype comprises at least one marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
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24. A method of selecting a treatment for a subject, the method comprising:
- obtaining a haplotype for the subject, wherein the haplotype comprises at least one marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
determining whether the haplotype is associated with an altered response profile for a clinical treatment; and
selecting the treatment if the haplotype indicates that the subject is more likely to have an improved response profile to the clinical treatment in question.
- obtaining a haplotype for the subject, wherein the haplotype comprises at least one marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
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25. A method of identifying haplotypes associated with altered outcome to a treatment for schizophrenia (SZ), schizotypal personality disorder (SPD), schizoaffective disorder (SD), or bipolar disorder (BD), the method comprising obtaining a haplotype for a subject, wherein the haplotype comprises at least one marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
- obtaining data regarding response to a treatment in the subject; and
correlating the haplotype with a response to the clinical treatment. - View Dependent Claims (26, 27, 28)
- obtaining data regarding response to a treatment in the subject; and
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29. A method of providing information regarding one or more of the following:
- a subject'"'"'s risk of developing schizophrenia (SZ) or bipolar disorder (BD); and
clinical response to antipsychotic medications, the method comprising;
obtaining a sample from the subject at a first site;
transferring the sample to a second site for analysis, wherein the analysis provides data regarding the identity, presence or absence of at least one test marker that is listed in Table A or is in linkage disequilibrium with a marker listed in Table A;
analyzing the data for potential impact on one or more of the following;
a subject'"'"'s risk of developing schizophrenia (SZ) or bipolar disorder (BD); and
clinical response to antipsychotic medications; and
transferring the results of the analysis to one or more of the following;
a health care provider;
the subject;
a healthcare payer;
or a clinical trial sponsor. - View Dependent Claims (30)
- a subject'"'"'s risk of developing schizophrenia (SZ) or bipolar disorder (BD); and
Specification