Methods for assessing risk of developing a viral disease using a genetic test
This document provides methods and materials related to treating a disease. For example, this document provides methods for treating a subject's disease based on identifying the risk of progressive multifocal leukoencephalopathy PML using a genetic test.
1. A method of treating a condition in a subject in need of immunosuppressive therapy, comprising: administering a therapeutically effective amount of dimethyl fumarate to the subject, wherein the subject has a decreased risk of progressive multifocal leukoencephalopathy (PML) due to an infection of the brain by John Cunningham virus (JCV), wherein the subject's decreased risk is associated with the absence of one or more genetic variations in the subject, wherein the subject has been tested for a presence of the one or more genetic variations with a genetic assay and has been identified as not having the one or more genetic variations, wherein the one or more genetic variations disrupts or modulates an IFIH1 gene, an IGLL1 gene, a PLCG2 gene, a TCIRG1 gene, a STXBP2 gene, a GFI1 gene, a HIVEP3 gene, a PKHD1 gene, an ATM gene, a DNER gene, a LIG1 gene, a LRBA gene, a TAP1 gene, a SERPIN gene or a NQO2 gene.
2. The method of claim 1 , wherein the condition is multiple sclerosis.
3. The method of claim 1 , wherein the one or more genetic variations have an odds ratio (OR) of 2 or more, and wherein the OR is:
[ D D /D N ]/[ N D /N N ],
wherein:
D D is the number of subjects in a diseased cohort of subjects with the one or more genetic variations;
D N the number of subjects in the diseased cohort without the one or more genetic variations;
N D is the number of subjects in a non-diseased cohort of subjects with the one or more genetic variations; and
N N is the number of subjects in the non-diseased cohort without the one or more genetic variations; and
wherein the diseased cohort of subjects have PML and the non-diseased cohort of subjects do not have PML.
4. The method of claim 1 , wherein the one or more genetic variations comprises chr22:23915583 T>C; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
5. The method of claim 1 , wherein the one or more genetic variations comprises chr2:163136505 C>G; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
6. The method of claim 1 , wherein the one or more genetic variations comprises chr11:67818269 G>A; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
7. The method of claim 1 , wherein the one or more genetic variations comprises chr22:23915745 G>A; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
8. The method of claim 1 , wherein the one or more genetic variations comprises chr16:81942175 A>G; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
9. The method of claim 1 , wherein the one or more genetic variations comprises chr19:7712287 G>C; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
10. The method of claim 1 , wherein the one or more genetic variations comprises chr1:92946625 G>C; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
11. The method of claim 1 , wherein the one or more genetic variations comprises chr1:42047208 C>G; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
12. The method of claim 1 , wherein the one or more genetic variations comprises chr6:51798908 C>T; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.
13. The method of claim 1 , wherein the one or more genetic variations comprises an SNV in an IFIH1 gene, an IGLL1 gene, a PLCG2 gene, a TCIRG1 gene, a STXBP2 gene, a GFI1 gene, a HIVEP3 gene, a PKHD1 gene, an ATM gene, a DNER gene, a LIG1 gene, a LRBA gene or a TAP1 gene.
14. The method of claim 1 , wherein a first genetic variation of the one or more genetic variations disrupts or modulates an IFIH1 gene, an IGLL1 gene, a PLCG2 gene, a TCIRG1 gene, a STXBP2 gene, a GFI1 gene, a HIVEP3 gene, a PKHD1 gene, an ATM gene, a DNER gene, a LIG1 gene, a LRBA gene, a TAP1 gene, a SERPIN gene or a NQO2 gene; and wherein a second genetic variation of the one or more genetic variations disrupts or modulates a corresponding gene according to Tables 3, 6, 25A, 25B, and 26.
15. The method of claim 3 , wherein the diseased cohort of subjects, the non-diseased cohort of subjects, or both cohorts of subjects are ethnically matched.
16. The method of claim 1 , wherein the subject has been identified as not having one or more other genetic variations that disrupt or modulate a corresponding gene according to Tables 1, 3, 6-10 and 19-24.
17. The method of claim 1 , wherein the subject has been tested with a JCV-antibody test, a CD62L test, or a CSF IgM oligoclonal bands test.
18. The method of claim 1 , wherein prior to testing the subject for the presence of the one or more genetic variations with the genetic assay the method further comprises obtaining biological samples from subjects with PML and (a) confirming each biological sample is not a duplicate of any other biological sample based on nucleic acid information of the biological samples or (b) determining a sex genotype for each biological sample based on nucleic acid information of the biological samples, and confirming the sex genotype of each biological sample is the same as a sex phenotype of the subject with PML from which the biological sample was obtained.
19. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates an IFIH1 gene.
20. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates an IGLL1 gene.
21. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a PLCG2 gene.
22. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates, a TCIRG1 gene.
23. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a STXBP2 gene.
24. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a GFI1 gene.
25. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates, a HIVEP3 gene.
26. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a PKHD1 gene.
27. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates an ATM gene.
28. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a DNER gene.
29. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a LIG1 gene.
30. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a LRBA gene.
31. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a TAP1 gene.
32. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a SERPIN gene.
33. The method of claim 1 , wherein the one or more genetic variations disrupts or modulates a NQO2 gene.
34. The method of claim 1 , wherein the condition is a relapsing form of multiple sclerosis.
35. The method of claim 1 , wherein the condition is relapsing-remitting multiple sclerosis (RRMS).
36. The method of claim 1 , wherein the condition is psoriasis.