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Supplementary Table 2:
From:- Carter C.J. Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: Cytomegalovirus, Influenza, Herpes simplex, Rubella, and T.Gondii, Schiz Bull, in press, 2008
A summary of the human genes implicated in infection by various species of virus and pathogen.
The data are a summary of association data stored at the HugeNet Phenopedia and of medline searches.
Genes also implicated in schizophrenia are highlighted in bold.
Wei Yu, Melinda Clyne, Anja Wulf, Ajay Yesupriya, Marta Gwinn, and Muin J. Khoury. Phenopedia. HuGE Navigator. Available at: Hugenavigator
Updates in progress | Influenza |
HSV-1 |
HHV-6 |
Herpesviridae infections |
Helicobacter pylori | Cytomegalovirus |
Toxoplasmosis |
No genetic studies found for Rubella |
MBL2, IL10 1 HLA-DRB1 2 IL6 3,4 |
APOE 5 DEFB1 Tesse et al, 2009 HLA-B 6 IL10 7 MICB 7 IL18RAP 8 LTF 9 KIR2DL2/ KIR2DS2 10 TLR2 11 MBL 12 |
TP53 13 MHC2TA 14 |
APOE 15 CCR5 16 CTLA4 17 HLA-DRB1 18 IL4 19 19,20 IL10 21 TNF 22 23 IL1A, TGFB1 24 MHC2TA 14 HLA-A 25 IFNG 26 SLC11A1 27 IL8RB, IL13 28. IL6, IL12A 19 FCGR3A 29 |
CD14 Virta et al, 2008 | DEFB1 Tesse et al, 2009 HLA-B 30 HLA-DRB1 31 IL1RN 32 IL10 33 IL12B 34 IL18, IL18R1, IL18RAP 8 TNF 34 MBL, TLR4 35,36 TLR2 37 GJB2 38 MICA 39 |
HLA-DRB1 40 ABCA4 Jamieson et al, 2009 CCR5 Ashton et al, 2002 COL2A1 Jamieson et al, 2009 IFNG Memorias et al, 2009 IL10 Cordeiro et al, 2008 TLR9 Memorias et al, 2009 HLA-DQB*0402 and DRB1*08 in HIV infected patients Habegger et al, 2005 |
Schizophrenia-related genes: N and % |
3 / 4 (75%) |
5 / 10 (50%) |
1 / 2 (50%) |
7 / 18 (39%) |
9 / 14 (64%) |
1/1 |
A linkage study has identified a marker (D21S409) at 21q21.1 related to HSV-1 infection 41 . This chromosomal region has also been implicated in schizophrenia 42,43,44 .
1. Tang, Y. W., Li, H., Wu, H., Shyr, Y., and Edwards, K. M. Host single-nucleotide polymorphisms and altered responses to inactivated influenza vaccine. J Infect.Dis. 2007; 196: 1021-1025.
2. Gelder, C. M., Lambkin, R., Hart, K. W., Fleming, D., Williams, O. M., Bunce, M. et al. Associations between human leukocyte antigens and nonresponsiveness to influenza vaccine. J Infect.Dis. 2002; 185: 114-117.
3. Mysliwska, J., Wieckiewicz, J., Hak, L., Siebert, J., Rogowski, J., Szyndler, K. et al. Long-term prognosis after coronary bypass surgery depends on interleukin 6 polymorphism and past acute infections. Int.J Cardiol. 2007; 118: 421-422.
4. Newton-Nash, D. K. and Eckels, D. D. Differential effect of polymorphism at HLA-DR1 beta-chain positions 85 and 86 on binding and recognition of DR1-restricted antigenic peptides. J Immunol. 1993; 150: 1813-1821.
5. Itzhaki, R. F. and Wozniak, M. A. Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer's disease and other disorders. Prog.Lipid Res. 2006; 45: 73-90.
6. Zernich, D., Purcell, A. W., Macdonald, W. A., Kjer-Nielsen, L., Ely, L. K., Laham, N. et al. Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion. J Exp.Med 2004; 200: 13-24.
7. Hurme, M., Haanpaa, M., Nurmikko, T., Wang, X. Y., Virta, M., Pessi, T. et al. IL-10 gene polymorphism and herpesvirus infections. J Med Virol. 2003; 70 Suppl 1: S48-S50.
8. Shirts, B. H., Wood, J., Yolken, R. H., and Nimgaonkar, V. L. Comprehensive evaluation of positional candidates in the IL-18 pathway reveals suggestive associations with schizophrenia and herpes virus seropositivity. Am.J Med Genet.B Neuropsychiatr.Genet. 2007;
9. Keijser, S., Jager, M. J., Dogterom-Ballering, H. C., Schoonderwoerd, D. T., de Keizer, R. J., Krose, C. J. et al. Lactoferrin Glu561Asp polymorphism is associated with susceptibility to herpes simplex keratitis. Exp.Eye Res. 2008; 86: 105-109.
10. Estefania, E., Gomez-Lozano, N., Portero, F., de Pablo, R., Solis, R., Sepulveda, S. et al. Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2. Tissue Antigens 2007; 70: 34-41.
11. Eid, A. J., Brown, R. A., and Razonable, R. R. Toll-like receptor-2 Arg753Gln polymorphism and herpes virus infections in transplantation. Transplantation 2006; 82: 1383-1385.
12. Tang, Y. W., Cleavinger, P. J., Li, H., Mitchell, P. S., Smith, T. F., and Persing, D. H. Analysis of candidate-host immunogenetic determinants in herpes simplex virus-associated Mollaret's meningitis. Clin.Infect.Dis. 2000; 30: 176-178.
13. Leite, J. L., Manfrinatto, J. A., Mazzali, M., and Ward, L. S. Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients. Transpl.Int. 2006; 19: 732-737.
14. Martinez, A., Alvarez-Lafuente, R., Mas, A., Bartolome, M., Garcia-Montojo, M., de, Las Heras, V et al. Environment-gene interaction in multiple sclerosis: human herpesvirus 6 and MHC2TA. Hum.Immunol. 2007; 68: 685-689.
15. Lin, W. R., Wozniak, M. A., Esiri, M. M., Klenerman, P., and Itzhaki, R. F. Herpes simplex encephalitis: involvement of apolipoprotein E genotype. J Neurol.Neurosurg.Psychiatry 2001; 70: 117-119.
16. Bogunia-Kubik, K., Jaskula, E., and Lange, A. The presence of functional CCR5 and EBV reactivation after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant. 2007; 40 : 145-150.
17. Parks, C. G., Cooper, G. S., Hudson, L. L., Dooley, M. A., Treadwell, E. L., St Clair, E. W. et al. Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype. Arthritis Rheum. 2005; 52: 1148-1159.
18. Gaya, A., Esteve, A., Casabona, J., McCarthy, J. J., Martorell, J., Schulz, T. F. et al. Amino acid residue at position 13 in HLA-DR beta chain plays a critical role in the development of Kaposi's sarcoma in AIDS patients. AIDS 2004; 18: 199-204.
19. Brown, E. E., Fallin, M. D., Goedert, J. J., Hutchinson, A., Vitale, F., Lauria, C. et al. Host immunogenetics and control of human herpesvirus-8 infection. J Infect.Dis. 2006; 193: 1054-1062.
20. Krol, A., Lensen, R., Veenstra, J., Prins, M., Schuitemaker, H., and Coutinho, R. A. Impact of CCR5 Delta32/+ deletion on herpes zoster among HIV-1-infected homosexual men. Eur.J Epidemiol. 2006; 21: 469-473.
21. da Silva, G. N., Bacchi, M. M., Rainho, C. A., and de Oliveira, D. E. Epstein-Barr virus infection and single nucleotide polymorphisms in the promoter region of interleukin 10 gene in patients with Hodgkin lymphoma. Arch.Pathol.Lab Med 2007; 131: 1691-1696.
22. Wu, M. S., Huang, S. P., Chang, Y. T., Shun, C. T., Chang, M. C., Lin, M. T. et al. Tumor necrosis factor-alpha and interleukin-10 promoter polymorphisms in Epstein-Barr virus-associated gastric carcinoma. J Infect.Dis. 2002; 185: 106-109.
23. Haanpaa, M., Nurmikko, T., and Hurme, M. Polymorphism of the IL-10 gene is associated with susceptibility to herpes zoster. Scand.J Infect.Dis. 2002; 34: 112-114.
24. Hatta, K., Morimoto, A., Ishii, E., Kimura, H., Ueda, I., Hibi, S. et al. Association of transforming growth factor-beta1 gene polymorphism in the development of Epstein-Barr virus-related hematologic diseases. Haematologica 2007; 92: 1470-1474.
25. Niens, M., Jarrett, R. F., Hepkema, B., Nolte, I. M., Diepstra, A., Platteel, M. et al. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma. Blood 2007; 110: 3310-3315.
26. Lee, T. C., Savoldo, B., Barshes, N. R., Rooney, C. M., Heslop, H. E., Gee, A. P. et al. Use of cytokine polymorphisms and Epstein-Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients. Clin.Transplant. 2006; 20: 389-393.
27. Barshes, N. R., Lee, T. R., Goss, J. A., Goodpastor, S. E., Huls, M. H., Rooney, C. M. et al. Slc11a1 (formerly Nramp1) polymorphisms and susceptibility to post-transplant lymphoproliferative disease following pediatric liver transplantation. Transpl.Infect.Dis. 2006; 8 : 108-112.
28. Brown, E. E., Fallin, D., Ruczinski, I., Hutchinson, A., Staats, B., Vitale, F. et al. Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity. Cancer Epidemiol.Biomarkers Prev. 2006; 15: 926-934.
29. Brown, E. E., Fallin, M. D., Goedert, J. J., Chen, R., Whitby, D., Foster, C. B. et al. A common genetic variant in FCGR3A-V158F and risk of Kaposi sarcoma herpesvirus infection and classic Kaposi sarcoma. Cancer Epidemiol.Biomarkers Prev. 2005; 14: 633-637.
30. Burrows, J. M., Wynn, K. K., Tynan, F. E., Archbold, J., Miles, J. J., Bell, M. J. et al. The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV. Eur.J Immunol. 2007; 37: 946-953.
31. Du, J., Liu, J., Gu, J., and Zhu, P. HLA-DRB1*09 is associated with increased incidence of cytomegalovirus infection and disease after allogeneic hematopoietic stem cell transplantation. Biol.Blood Marrow Transplant. 2007; 13: 1417-1421.
32. Witkin, S. S., Gerber, S., and Ledger, W. J. Influence of interleukin-1 receptor antagonist gene polymorphism on disease. Clin.Infect.Dis. 2002; 34: 204-209.
33. Alakulppi, N. S., Kyllonen, L. E., Salo, H. M., Partanen, J., Salmela, K. T., and Laine, J. T. The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation. Transpl.Immunol. 2006; 16: 258-262.
34. Price, P., Morahan, G., Huang, D., Stone, E., Cheong, K. Y., Castley, A. et al. Polymorphisms in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases. AIDS 2002; 16: 2043-2047.
35. Cervera, C., Lozano, F., Saval, N., Gimferrer, I., Ibanez, A., Suarez, B. et al. The influence of innate immunity gene receptors polymorphisms in renal transplant infections. Transplantation 2007; 83: 1493-1500.
36. Ducloux, D., Deschamps, M., Yannaraki, M., Ferrand, C., Bamoulid, J., Saas, P. et al. Relevance of Toll-like receptor-4 polymorphisms in renal transplantation. Kidney Int. 2005; 67: 2454-2461.
37. Kijpittayarit, S., Eid, A. J., Brown, R. A., Paya, C. V., and Razonable, R. R. Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation. Clin.Infect.Dis. 2007; 44: 1315-1320.
38. Ross, S. A., Novak, Z., Kumbla, R. A., Zhang, K., Fowler, K. B., and Boppana, S. GJB2 and GJB6 mutations in children with congenital cytomegalovirus infection. Pediatr.Res. 2007; 61: 687-691.
39. Huang, B. S., Luo, Q. Z., Li, L. X., Mei, B., Zou, Y. Z., Wu, L. X. et al. [MICA*008/A5.1 allele and HCMV infection in kidney transplanted donees of Hunan Han nationality]. Zhong.Nan.Da.Xue.Xue.Bao.Yi.Xue.Ban. 2006; 31: 479-482.
40. Habegger, de Sorrentino, Lopez, R., Motta, P., Marinic, K., Sorrentino, A., Iliovich, E. et al. HLA class II involvement in HIV-associated Toxoplasmic encephalitis development. Clin.Immunol. 2005; 115: 133-137.
41. Hobbs, M. R., Jones, B. B., Otterud, B. E., Leppert, M., and Kriesel, J. D. Identification of a herpes simplex labialis susceptibility region on human chromosome 21. J Infect.Dis. 2008; 197: 340-346.
42. Fallin, M. D., Lasseter, V. K., Wolyniec, P. S., McGrath, J. A., Nestadt, G., Valle, D. et al. Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22. Am.J Hum.Genet. 2003; 73: 601-611.
43. Goodman, A. B. Elevated risks for amyotrophic lateral sclerosis and blood disorders in Ashkenazi schizophrenic pedigrees suggest new candidate genes in schizophrenia. Am.J Med Genet. 1994; 54: 271-278.
44. Takhar, J., Malla, A. K., Siu, V., MacPherson, C., Fan, Y. S., and Townsend, L. An interstitial deletion of the long arm of chromosome 21 in a case of a first episode of psychosis. Acta Psychiatr.Scand. 2002; 106: 71-74.
Last update: July 27, 2015