Methods for assessing risk of developing a viral disease 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 an immunosuppressive agent 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 a C8B gene, a FCN2 gene, or a LY9 gene.

2. The method of claim 1 , wherein the condition is lupus.

3. The method of claim 2 , wherein the condition is systemic lupus erythematosus.

4. The method of claim 1 , wherein the immunosuppressive agent is belimumab, teriflunomide, fingolimod, rituximab, daclizumab, obinutuzumab, ocrelizumab, ofatumumab, siponimod or any combination thereof.

5. The method of claim 4 , wherein the immunosuppressive agent is belimumab.

6. The method of claim 1 , wherein the one or more genetic variations comprises chr1:57409459 C>A, chr9:137779251 G>A, or chr1:160769595 AG>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 disrupts or modulates a C8B gene.

8. The method of claim 7 , wherein the one or more genetic variations comprises chr1:57409459 C>A, 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 disrupts or modulates a FCN2 gene.

10. The method of claim 9 , wherein the one or more genetic variations comprises chr9:137779251 G>A, 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 disrupts or modulates a LY9 gene.

12. The method of claim 11 , wherein the one or more genetic variations comprises chr1:160769595 AG>A, wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

13. The method of claim 1 , wherein (i) the condition is lupus or systemic lupus erythematosus, (ii) the immunosuppressive agent is belimumab, and (iii) the one or more genetic variations comprises chr1:57409459 C>A, chr9:137779251 G>A, or chr1:160769595 AG>A; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

14. The method of claim 1 , wherein the subject has been tested with a genetic assay for a genetic variation that disrupts or modulates a STXBP2 gene and wherein the subject has been identified as not having a genetic variation that disrupts or modulates a STXBP2 gene.

15. The method of claim 14 , wherein the genetic variation that disrupts or modulates a STXBP2 gene comprises chr19:7712287 G>C; wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

16. The method of claim 1 , wherein the subject has been tested with a genetic assay for at least two of:

(i) a genetic variation that disrupts or modulates a STXBP2 gene,

(ii) a genetic variation that disrupts or modulates a C8B gene,

(iii) a genetic variation that disrupts or modulates a FCN2 gene, and

(iv) a genetic variation that disrupts or modulates a LY9 gene; and

wherein the subject has been identified as not having at least two of (i)-(iv).

17. The method of claim 1 , wherein the subject has been tested with a genetic assay for a presence of a genetic variation that disrupts or modulates a C8B gene, a genetic variation that disrupts or modulates a FCN2 gene, and a genetic variation that disrupts or modulates a LY9 gene, and wherein the subject has been identified as:

(i) not having a genetic variation that disrupts or modulates a C8B gene

(ii) not having a genetic variation that disrupts or modulates a FCN2 gene; and

(iii) not having a genetic variation that disrupts or modulates a LY9 gene.

18. The method of claim 1 , wherein the subject has been tested with a genetic assay for a presence of a genetic variation that disrupts or modulates a STXBP2 gene, a C8B gene, a genetic variation that disrupts or modulates a FCN2 gene, and a genetic variation that disrupts or modulates a LY9 gene, and wherein the subject has been identified as:

(i) not having a genetic variation that disrupts or modulates a C8B gene,

(ii) not having a genetic variation that disrupts or modulates a FCN2 gene,

(iii) not having a genetic variation that disrupts or modulates a LY9 gene, and

(iv) not having a genetic variation that disrupts or modulates a STXBP2 gene.

19. The method of claim 1 , wherein the one or more genetic variations comprise an SNV in a gene selected from the group consisting of C8B, FCN2 and LY9.

20. 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, 19-24, 28A, 29, 31, 34-36, 40, 42, 47 and 48.

21. 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.

22. The method of claim 1 , wherein the method further comprises testing the subject for the presence of the one or more genetic variations with the genetic assay prior to the administering.

23. The method of claim 22 , wherein the genetic assay comprises microarray analysis, PCR, sequencing, nucleic acid hybridization, or any combination thereof.

24. The method of claim 22 , 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.