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 that has a potential to induce progressive multifocal leukoencephalopathy (PML) due to an infection of the brain by John Cunningham virus (JCV), wherein the subject has been tested for a presence of 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 disrupt or modulate an ACD gene, a BLK gene, a C2 gene, a CD36 gene, a CFHR4 gene, a CFTR gene, a FAT4 gene, a KMT2D gene, a LPIN2 gene, a MX1 gene, a NCF2 gene, an OAS3 gene, a PLAUR gene, a PLD1 gene, a PLXNB1 gene, a PRRC2A gene, a RANBP2 gene, a SH3BP2 gene or a TBC1D17 gene; and wherein the administering is based on the identification of the subject as not having the one or more genetic variations.

2. The method of claim 1 , wherein the method comprises testing the subject for the presence of the one or more genetic variations with the genetic assay prior to the administering, wherein the genetic assay comprises microarray analysis, PCR, sequencing, nucleic acid hybridization, or any combination thereof.

3. The method of claim 1 , wherein the genetic assay comprises whole exome sequencing or whole genome sequencing.

4. 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.

5. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate an ACD gene, a BLK gene, a CD36 gene, a CFHR4 gene, a CFTR gene, a FAT4 gene, a KMT2D gene, a MX1 gene, a NCF2 gene, an OAS3 gene, a PLAUR gene, a PLD1 gene, a PLXNB1 gene, a PRRC2A gene, a RANBP2 gene, or a TBC1D17 gene.

6. The method of claim 5 , wherein the one or more genetic variations comprise two or more genetic variations.

7. The method of claim 6 , wherein the one or more genetic variations comprises at least 5 genetic variations.

8. The method of claim 1 , wherein the genetic assay comprises determining a sex genotype for a biological sample from the subject and confirming the sex genotype of the biological sample is the same as a sex phenotype of the subject.

9. 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, 28A, 29, 31, 34-36, 40, 47 and 48.

10. The method of claim 1 , wherein the subject is identified as not having one or more other genetic variations that disrupt or modulate a corresponding gene according to Tables 19-24, 40 and 42.

11. The method of claim 6 , wherein a second genetic variation of the one or more genetic variations disrupts or modulates a corresponding gene according to Tables 1, 3, 6-10, 28A, 29, 31, 34-36, 40, 47 and 48.

12. The method of claim 6 , wherein a second genetic variation of the one or more genetic variations disrupts or modulates a corresponding gene according to Tables 19-24, 40 and 42.

13. The method of claim 1 , wherein the condition is Crohn's disease, multiple sclerosis or a relapsing form of multiple sclerosis.

14. The method of claim 5 , wherein the one or more genetic variations comprises chr16:67694044 C>T, chr16:67694078 G>T, chr8: 11400805 C>A, chr8:11415492A>C, chr8:11400849 C>T, chr8:11412934 G>A, chr8:11418856 C>T, chr8:11407690 C>T, chr7:80300449 T>G, chr1: 196871610 A>T, chr7: 117230454 G>C, chr7:117232223 C>T, chr7:117232086 G>A, chr7: 117246776 T>C, chr4: 126239986 C>T, chr4:126412154 G>A, chr4:126373570 C>T, chr4: 126412106 C>G, chr4: 126238090 G>T, chr4: 126239241 G>A, chr4:126411493 C>T, chr4: 126241248 C>G, chr4: 126239623 G>A, chr4:126239253 G>C, chr4:126328170 C>T, chr4:126372003 A>G, chr4:126412226 G>A, chr4:126336758 G>A, chr4: 126239421 C>T, chr4:126241785 G>A, chr4: 126389832 G>A, chr4:126240377 G>T, chr4: 126408663 A>G, chr4:126372975 A>C, chr4:126237697 A>C, chr4:126240968 A>T, chr4:126411179 C>T, chr4:126241720 T>C, chr4:126240255 A>G, chr4:126240390 A>G, chr4:126238305 C>A, chr4: 126336851 G>A, chr4: 126412634 C>G, chr12:49421811 C>A, chr12:49433533 G>C, chr12:49440564 C>T, chr12:49433083 G>A, chr12:49421042 C>T, chr12:49428694 T>C, chr21:42813652 C>A, chr21:42830657 G>A, chr21:42807815 A>G, chr21:42830468 G>A, chr21:42817460 C>T, chr21:42812952 G>A, chr21:42815731 G>A, chr21:42807881 G>A, chr1: 183532364 T>A, chr12:113403675 C>T, chr12:113405825 G>A, chr12: 113376543 C>CCAAAGGG, chr19:44153248 T>C, chr3:171455697 G>C, chr3:171455739A>G, chr3:171321023 C>T, chr3:171379953 C>T, chr3:171431726 C>G, chr3:48461135 C>T, chr3:48457498 G>C, chr3:48463544 G>A, chr6:31601735 G>A, chr6:31604894 C>T, chr6:31600118 G>A, chr6:31597469 A>C, chr6:31598524 G>A, chr6:31593603 A>G, chr6:31602967 G>A, chr6:31600558 C>T, chr6:31597451 G>A, chr6:31600708 G>A, chr6:31603045 A>G, chr6:31604591 C>T, chr6:31605278 C>T, chr6:31595926 C>T, chr6:31595795 C>T, chr6:31604610 T>C, chr6:31599370 G>C, chr6:31605016 T>C, chr6:31600696 G>A, chr2:109381493 G>C, chr2:109382448 C>T, chr2:109384800 C>T, chr19:50394219 G>C, chr19:50394205 T>C, or chr19:50385633 G>C.

15. The method of claim 1 , wherein the subject is further identified as not having one or more genetic variations that disrupt or modulate a gene selected from the group consisting of C8B, LY9, FCN2, and STXBP2.

16. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate an ACD gene and wherein the one or more genetic variations comprise chr16:67694044 C>T or chr16:67694078 G>T.

17. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a BLK gene and wherein the one or more genetic variations comprise chr8:11400805 C>A, chr8: 11415492A>C, chr8:11400849 C>T, chr8: 11412934 G>A, chr8:11418856 C>T, or chr8:11407690 C>T.

18. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a CD36 gene and wherein the one or more genetic variations comprises chr7:80300449 T>G.

19. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a CFHR4 gene and wherein the one or more genetic variations comprises chr1: 196871610 A>T.

20. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a CFTR gene and wherein the one or more genetic variations comprise chr7:117230454 G>C, chr7:117232223 C>T, chr7:117232086 G>A, or chr7:117246776 T>C.

21. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a FAT4 gene and wherein the one or more genetic variations comprise chr4:126239986 C>T, chr4:126412154 G>A, chr4: 126373570 C>T, chr4: 126412106 C>G, chr4:126238090 G>T, chr4: 126239241 G>A, chr4: 126411493 C>T, chr4:126241248 C>G, chr4:126239623 G>A, chr4: 126239253 G>C, chr4:126328170 C>T, chr4: 126372003 A>G, chr4:126412226 G>A, chr4: 126336758 G>A, chr4: 126239421 C>T, chr4: 126241785 G>A, chr4:126389832 G>A, chr4:126240377 G>T, chr4: 126408663 A>G, chr4:126372975 A>C, chr4:126237697 A>C, chr4:126240968 A>T, chr4:126411179 C>T, chr4: 126241720 T>C, chr4:126240255 A>G, chr4:126240390 A>G, chr4:126238305 C>A, chr4: 126336851 G>A, or chr4:126412634 C>G.

22. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a KMT2D gene and wherein the one or more genetic variations comprise chr12:49421811 C>A, chr12:49433533 G>C, chr12:49440564 C>T, chr12:49433083 G>A, chr12:49421042 C>T, or chr12:49428694 T>C.

23. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a MX1 gene and wherein the one or more genetic variations comprise chr21:42813652 C>A, chr21:42830657 G>A, chr21:42807815 A>G, chr21:42830468 G>A, chr21:42817460 C>T, chr21:42812952 G>A, chr21:42815731 G>A, or chr21:42807881 G>A.

24. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a NCF2 gene and wherein the one or more genetic variations comprises chr1:183532364 T>A.

25. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a OAS3 gene and wherein the one or more genetic variations comprise chr12:113403675 C>T, chr12:113405825 G>A, or chr12:113376543 C>CCAAAGGG.

26. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a PLAUR gene and wherein the one or more genetic variations comprises chr19:44153248 T>C.

27. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a PLD1 gene and wherein the one or more genetic variations comprise chr3:171455697 G>C, chr3:171455739A>G, chr3:171321023 C>T, chr3: 171379953 C>T, or chr3:171431726 C>G.

28. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a PLXNB1 gene and wherein the one or more genetic variations comprise chr3:48461135 C>T, chr3:48457498 G>C, or chr3:48463544 G>A.

29. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a PRRC2A gene and wherein the one or more genetic variations comprise chr6:31601735 G>A, chr6:31604894 C>T, chr6:31600118 G>A, chr6:31597469 A>C, chr6:31598524 G>A, chr6:31593603 A>G, chr6:31602967 G>A, chr6:31600558 C>T, chr6:31597451 G>A, chr6:31600708 G>A, chr6:31603045 A>G, chr6:31604591 C>T, chr6:31605278 C>T, chr6:31595926 C>T, chr6:31595795 C>T, chr6:31604610 T>C, chr6:31599370 G>C, chr6:31605016 T>C, or chr6:31600696 G>A.

30. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a RANBP2 gene and wherein the one or more genetic variations comprise chr2:109381493 G>C, chr2:109382448 C>T, or chr2:109384800 C>T.

31. The method of claim 1 , wherein the one or more genetic variations disrupt or modulate a TBC1D17 gene and wherein the one or more genetic variations comprise chr19:50394219 G>C, chr19:50394205 T>C, or chr19:50385633 G>C.