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 natalizumab therapy, comprising: administering a therapeutically effective amount of natalizumab 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 an 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 disrupt or modulate a gene selected from the group consisting of homo sapiens chromodomain helicase DNA binding protein 7 (CHD7), homo sapiens interferon induced with helicase C domain 1 (IFIH1), homo sapiens immunoglobulin lambda like polypeptide 1 (IGLL1), homo sapiens mitochondrial antiviral signaling protein (MAVS), homo sapiens phospholipase C gamma 2 (PLCG2), homo sapiens SHANK-associated RH domain interactor (SHARPIN), homo sapiens T-cell immune regulator 1, ATPase H+ transporting V0 subunit a3 (TCIRG1), and any combinations thereof, and

wherein the one or more genetic variations comprise chr8:61654298 T>A, chr2:163136505 C>G, chr22:23917192 G>T, chr20:3846397 C>T, chr16:81942175 A>G, chr8:145154222 G>A, chr11:67818269 G>A, chr8:145154824 A>C, chr22:23915745 G>A, chr20:3843027 C>A, or any combinations thereof, and wherein chromosome positions of the one or more genetic variations are defined with respect to UCSC hg19.

2. The method of claim 1 , wherein the condition is multiple sclerosis or a relapsing form of multiple sclerosis.

3. The method of claim 1 , wherein the one or more genetic variations have an odds ratio (OR) of 3 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 is 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,

wherein the diseased cohort of subjects have PML, and wherein the non-diseased cohort of subjects do not have PML.

4. 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.

5. The method of claim 4 , wherein the genetic assay has a diagnostic yield of at least 20%.

6. The method of claim 1 , wherein the one or more genetic variations comprise chr16:81942175 A>G.

7. The method of claim 1 , wherein the one or more genetic variations comprise chr8:145154222 G>A.

8. The method of claim 1 , wherein a first genetic variation of the one or more genetic variations disrupts or modulates a gene selected from the group consisting of CHD7, IFIH1, IGLL1, MAVS, PLCG2, SHARPIN, and TCIRG1; and wherein a second genetic variation of the one or more genetic variations disrupts or modulates a corresponding gene according to Tables 3 and 6.

9. The method of claim 1 , wherein the one or more genetic variations comprise chr2:163136505 C>G.

10. The method of claim 1 , wherein the one or more genetic variations comprise chr8:61654298 T>A.

11. The method of claim 1 , wherein the one or more genetic variations-comprise chr22:23917192 G>T.

12. The method of claim 1 , wherein the one or more genetic variations comprise chr20:3846397 C>T.

13. The method of claim 4 , wherein the genetic assay comprises microarray analysis, PCR, sequencing, nucleic acid hybridization, or any combinations thereof.

14. The method of claim 1 , wherein the subject has been tested with a JCV-antibody test.

15. The method of claim 14 , wherein the JCV-antibody test does not detect a presence of JCV.

16. 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.

17. 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.

18. The method of claim 3 , wherein the one or more genetic variations have an odds ratio (OR) of 6 or more.

19. The method of claim 1 , wherein the subject has been tested with a CD62L test or a CSF IgM oligoclonal bands test.

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 3 and 6.

21. The method of claim 1 , wherein the one or more genetic variations comprise chr11:67818269 G>A.

22. The method of claim 1 , wherein the one or more genetic variations comprise chr8:145154824 A>C.

23. The method of claim 1 , wherein the one or more genetic variations comprise chr22:23915745 G>A.

24. The method of claim 1 , wherein the one or more genetic variations comprise chr20:3843027 C>A.

25. The method of claim 1 , wherein the condition is Crohn's disease.

26. The method of claim 4 , 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 confirming each biological sample is not a duplicate of any other biological sample based on nucleic acid information of the biological samples.

27. The method of claim 4 , 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, 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.