Schizophrenia Research
Volume 47, Issue 1 , Pages 1-12 , 15 January 2001

Schizophrenia and HLA: a review

  • Padraig Wright

      Affiliations

    • Department of Psychological Medicine, Institute of Psychiatry and King's College Hospital, De Crespigny Park, London SE5 8AF, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44-171-9193129; fax: +44-171-7019044
    • ,
  • Vishwajit L. Nimgaonkar

      Affiliations

    • Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA
    • ,
  • Peter T. Donaldson

      Affiliations

    • Centre for Liver Research, The School of Clinical Medical Sciences, University of Newcastle, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK
    • ,
  • Robin M. Murray

      Affiliations

    • Department of Psychological Medicine, Institute of Psychiatry and King's College Hospital, De Crespigny Park, London SE5 8AF, UK

Received 10 July 1998 ,Accepted 28 January 2000.

References 

  1. Adler S, Vasile RG, Yunis E, Shapiro R. HLA in psychiatric and control subjects. A comparative study of HLA antigen frequencies in schizophrenic schizoaffective and control subjects. J. Psychiatr. Res. 1985;19:573–578
  2. Alexander RC, Coggiano M, Daniel DG, Wyatt RJ. HLA antigens in schizophrenia. Psychiatr. Res. 1990;31:221–233
  3. Amar A, Hohar M, Tiwari S, Broutbar C. HLA and schizophrenia in Israel. Isr. J. Med. Sci. 1988;24:28–31
  4. Antonarakis SE. Schizophrenia susceptibility and chromosome 6p24-22. letter Nat. Genet. 1995;11:235–236
  5. American Psychiatric Association. Diagnostic and Statistical manual od mental disorders. 2nd ed, 1980, 3rd ed. 1987, 4th ed. 1994. Washington DC: APA; 1980, 1987, 1994;
  6. Arinami T, Otsuka Y, Hamaguchi H, et al.  Evidence suporting an association between the DRB1 gene and schizophrenia in Japanese. Schizophr. Res. 1998;32:81–86
  7. Asaka A, Okazaki Y, Namura I, Juji T. Study of HLA antigens among Japanese schizophrenics. Br. J. Psychiatry. 1981;138:498–500
  8. Baisch JM. Analysis of HLA-DQ genotypes and susceptibility in insulin dependent diabetes mellitus. New Engl. J. Med. 1990;1990:1836–1841
  9. Bartfeld H, Pollack MS, Cunningham Rundles S, Donnenfeld H. HLA frequencies in amyotrophic lateral sclerosis. Arch. Neurol. 1982;39:270–271
  10. Behan WH, Behan PO, Dick HA. HLA B8 in polymyositis. New Engl. J. Med. 1978;298:1260–1261
  11. Bennahum DA, Troup GM, Rada RT, Kellner R, Kyner T. HLA antigens in schizophrenic and manic-depressive mental disorders. Clin. Res. 1977;25:114
  12. Bleuler E. Dementia praecox or the group of schizphrenias. (Translator) Joeseph Zankin).. New York: International Univeristies Press; 1950;
  13. Blackwood DH, Muir WJ, Stephenson A, Wentzel J, Ad'hiah A, Walker MJ, et al. Reduced expression of HLA B35 in schizophrenia. Psychiatr. Genet. 1996;6:51–59
  14. Brewerton DA, Caffrey M, Hart FD, James DCO, Nicholls A, Sturrock RD. Ankylosing spondylitis and HLA B27. Lancet. 1973;i:904–907
  15. Burch PRD. Schizophrenia: some new aetiological considerations. Br. J. Psychiatry. 1964;110:818–896
  16. Campbell DR, Trowsdale J. Map of the human MHC. Immunol. Today. 1993;14:349–352
  17. Campion D, Lebiyer M, Hillaire D. Relationship of HLA to schizophrenia not supported in multiplex families. Psychiatr. Genet. 1991;2:69
  18. Cazzullo CL, Smeraldi E, Penati G. The leucocyte antigenic system HL-A as possible genetic marker of schizophrenia. Br. J. Psychiatry. 1974;125:612–615
  19. Couillion P, Fellous M. Recherche d'une correlation entre is systeme antigenique HL-A et les recepteurs viraux trois enterovirus a l'aide de l'hybridisation cellulaire. Soc. Biol. 1974;168:180–186
  20. Crowe R, Thompson J, Flink R, Weinberger B. HLA antigens and schizophrenia. Arch. Gen. Psychiatry. 1979;30:231–233
  21. Dawkins RL, Kay PH, Garlepp MJ, Christiansen FT. Immunogenetics of spotaneous drug induced and experimental myasthenia gravis. Ann. NY Acad. Sci. 1987;505:398–406
  22. de Vries RRP. HLA and disease from epidemiology to immunotherapy. Eur. J. Clin. Invest. 1991;22:1–8
  23. DiMichele et al (1990) quoted in Hawi et al, 1999
  24. Dorman JS, LaPorte RE, Stone RA, Trucco M. Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA DQ B chain. Proc. Natl. Acad. Sci. USA. 1990;87:7370–7374
  25. Eberhard G, Franzen G, Low B. Schizophrenia susceptibility and HLA antigens. Neuropsychobiology. 1975;1:211–217
  26. Eaton WW, Hayward C, Ram R. Schizophrenia and rheumatoid arthritis: a review. Schizophr. Res. 1992;6:181–192
  27. Feeney DJ, Pollard JD, McLeod JG, Stewart GJ, Doran TJ. HLA antigens in chronic inflammatory demyelinating polyneuropathy. J. Neurol. Neurosurg. Psychiatry. 1990;53:170–172
  28. Feighner JP, Robins E, Guze SB, Woodruff RA, Winokur G, Munoz R. Diagnostic criteria for use in psychiatric research. Arch. Gen. Psychiatry. 1972;26(1):57–63
  29. Finney GO. Juvenile onset diabetes and schizophrenia. Lancet. 1989;2:1214–1215
  30. Garlepp MJ. Immunogenetics of inflammatory myopathies. Balliere's Clin. Neurol. 1993;2:579–597
  31. Gattaz QWF, Beckmann H. HLA antigens and schizophrenia. Lancet. 1980;1:98–99
  32. Gorer PA. The genetic and antigen basis for tumour transplantation. J. Pathol. Bacteriol. 1937;44:691–697
  33. Gorodezky C, Varela B, Castro-Esacbor LE, Chavez nagrete A, Escabor Gutierrez A, Martinez Mata J. HLA DR antigens in Mexican patients with Guillain–Barre syndrome. J. Neuroimmunol. 1983;4:1–7
  34. Gibson S, Hawi Z, Straub RE, Walsh D, Kendler KS, Gill M. HLA and schizophrenia: refutation of reported associations with A9 (A23/A24) DR4 and DQbeta1∗0602. Am. J. Med. Genet. 1999;88(4):416–421
  35. Goudemand M, Goudemand J, Parquet PhJ, Fontan M. Psychoses schizophreniques et antigenes HLA. Encephale. 1981;7:609–622
  36. Gurling H, et al.  Schizophrenia susceptibility and chromosome 6p24-22. letter Nat. Genet. 1995;11:34–235
  37. Hawi Z, Gibson S, Straub RE, Walsh D, Kendler KS, Gill M. Schizophrenia and HLA: no association with PCR-SSOP typed classical loci in a large Irish familial sample. Am. J. Med. Genet. 1999;88(4):422–429
  38. Hill AVS, Allsop CEM, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, et al. Common West African HLA antigens are associated with protection from severe malaria. Nature. 1991;352:595–600
  39. Hillert J, Olerup O. HLA and MS. Neurology. 1993;43:2426–2427
  40. Honda Y. HLA and narcolepsy. In:  Honda Y,  Juji T editor. HLA in Narcolepsy. New York: Springer; 1988;p. 1988
  41. Ivanyi D, Ivanyi P, Zemek P. HLA Cw4 in paranoid schizophrenia. Tissue Antigens. 1977;9:41–44
  42. Ivanyi D, Zemek P, Ivanyi P. HLA antigens in schizophrenia. Tissue Antigens. 1976;8:217–220
  43. Ivanyi D, Zemek P, Ivanyi P. HLA antigens as possible markers of heterogeneity in schizophrenia. J. Immunogenet. 1978;5:165–172
  44. Ivanyi P, Droes J, Schreuder GM, D'Amaro J, van Rood JJ. A Search for association of HLA antigens with paranoid schizophrenia. A9 appears as a possible marker. Tissue Antigens. 1983;22(3):186–193
  45. Jacobsen LK, Mittleman BB, Kumra S, Lenane MC, Barracchini KC, Adams S, et al. HLA antigens in childhood onset schizophrenia. Psychiatry Res. 1998;78(3):123–132
  46. Jonsson EG, Zhang F, Nimgaonkar VL, Rudert WA, Sedvall GC. Lack of association between schizophrenia and HLA DQB1 alleles in a Swedish sample. Schizophr. Res. 1998;29(3):293–296
  47. Julien RA, Mercier P, Chouraqui P. Schizophreniques et systeme d'histocompatibilitie tissulaire. Mise en evidence de l'augmentation des antigenes A9 et Cw4 dans la schizophrenie paranoide. Ann. Med. Psychol. 1977;135:939–944
  48. Khalil I, Deschamps I, Lepage V, Al-Daccak R, Degos L, Hors J. Dose effect of cis and trans encoded HLA DQB alpha/beta heterodimers in IDDM susceptibility. Diabetes. 1992;41:378–384
  49. Klein J. Natural history of the Major Histocompatibility Complex. New York: John Wiley; 1986;
  50. Kott E, Livni E, Zamir R, Kuritzky A. Cell mediated immunity to polio and HLA antigens in amyotrophic lateral sclerosis. Neurology. 1979;29:1040–1044
  51. Kyner T, Bennahum DA, Troup GM, Rada RT, Kellner R. The HLA SD antigens and schizophrenia — a statistical analysis. Birth Defects. 1978;14:185–190original article series
  52. Luchins D, Torrey EF, Weinberger DR, Zalcman S, DeLisi L, Johnson A, et al. HLA antigens in schizophrenia: differences between patients with and without evidence of brain atrophy. Br. J. Psychiatry. 1980;136:243–248
  53. Macaubas C, Hallmayer J, Kalil J, Kimura A, Yasunaga S, Grumet FC, et al. Extensive polymorphism of a (CA)n microsatellite located in the HLA DQA1/DQB1 class II region. Human Immunol. 1995;42:209–220
  54. McGuffin P. Is schizophrenia an HLA associated disease?. Psychol. Med. 1979;9:721–728
  55. McGuffin P, Farmer AE, Rajah SM. Histocompatibility antigens and schizophrenia. Br. J. Psychiatry. 1978;132:149–151
  56. McGuffin P, Sturt E. Genetic markers in schizophrenia. Human Hered. 1986;36:65–88
  57. Mendlewicz WS, Verbanck P, Linkowski P, Govaerts A. HLA antigens in affective disorders and schizophrenia. J. Affect. Disord. 1981;3:17–24
  58. Metzer WS, Newton JEO, Steele R, Claybrook M, McMillan DE, Hayes S. HLA antigens and haplotypes in schizophrenia. Neuropsychiatry Neuropsychol. Behav. Neurol. 1988;1:40–46
  59. Miyanaga K, Machiyama Y, Juji T. Schizophrenic disorders and HLA-DR antigens. Biol. Psychiatry. 1984;19:121–129
  60. Moises HW, et al.  An international two stage genome wide search for schizophrenia susceptibility genes. Nat. Genet. 1995;11:321–324
  61. Mowry BJ, et al.  Schizophrenia susceptibility and chromosome 6p24-22.. letter Nat. Genet. 1995;11:233–234
  62. Muller N, Loebenfelder A, Lorenz A, Wank R, Ackenheil M. HLA Class II antigens in endogenous psychoses. Ann. NY Acad. Sci. 1992;650:322–325
  63. Mytilineos J, Scherer S, Opelz G. Comparison of RFLP DR beta and serological HLA-DR typing in 1500 individuals. Transplantation. 1990;50:870–873
  64. Nimgaonkar VL, Ganguli R, Rudert WA, Vavassori C, Rabin BS, Trucco M. A negative association of schizophrenia with an allele of the HLA DQB1 gene among African-Americans. Schizophr. Res. 1992;8:199–209
  65. Nimgaonkar VL, Rudert WA, Zhang XR, Trucco M, Ganguli R. Negative association of schizophrenia with HLA DQB1∗0602: evidence from a second African-American cohort. Schizophr. Res. 1997;23:81–86
  66. Nimgaonkar VL, Rudert WA, Zhang XR, Tsoi WF, Trucco M, Saha N. Further evidence for an association between schizophrenia and the the HLA DQB1 gene locus. Schizophr. Res. 1995;18:43–49
  67. Olerup O, Schaffer M, Hillert J, Sachs C. The narcolepsy associated DR15 DQ6 Dw2 haplotype has no unique HLA DQα or DQβ restriction fragments and does not extend to the HLA DP subregion. Immunogenetics. 1990;32:41–44
  68. Ozcan ME, Taskin R, Banoglu R, Babacan M, Tuncer E. HLA antigens in schizophrenia and mood disorders. Biol. Psychiatry. 1996;(10):891–895
  69. Perris C, Roman G, Wahlby L. HLA antigens in patients with schizophrenic syndromes. Neuropsychobiology. 1979;5:290–293
  70. Pugliese A, Gianani R, Moromisato R, Awdeh ZL, Alper CA, Erlich HA, et al. HLA DQB1∗0602 is associated with dominant protection from diabetes even among islet-cell antibody positive relatives of patients with IDDM. Diabetes. 1995;44:608–613
  71. Pugliese A, Solimena M, Awdeh ZL, Alper CA, Bugawan T, Erlich HA, et al. Association of HLA DQB1∗0201 with stiff man syndrome. J. Clin. Endocrinol. Metab. 1993;77:1550–1553
  72. Rabin, B., Ganguli, R., Boehmer, S., Kupfer, D., 1987. Association of HLA-DR6 with schizophrenia. Quoted in Nimgaonkar et al., 1992.
  73. Rammensee HG, Falk K, Rotzschke O. MHC molecules as peptide receptors. Curr. Opin. Immunol. 1993;5:35–44
  74. Roitt IM. Essential Immunology. Oxford: Blackwell Scientific; 1991;
  75. Rosler M, Bellaire W, Gressnich N, Giannitsis D, Jarovici A. HLA antigens in schizophrenia major depressive disorder and schizoaffective disorder. Med. Microbiol. Immunol. 1980;172:57–65
  76. Rudduck C, Franzen G, Low B, Rorsman B. HLA antigens and clinical subgroups of schizophrenia. Human Hered. 1984;34:18–26
  77. Rudduck C, Franzen G, Low B, Rorsman B. HLA antigens in patients with and without a family history of schizophrenia. Human Hered. 1984;34:291–296
  78. Sasaki T, Akaho R, Narita K, Okazaki Y, Okabe Y, Matsushita M, et al. Suport for an association between HLA-DR1 and schizophrenia in a Japanese population. Am. J. Med. Genet. Neuropsych. Genet. 2000;in press
  79. Sasaki T, Kuwata S, Dai XY, Nanko S, et al.  HLA DR types in Japanese schizophrenia: analysis by group-specific PCR amplification. Schizophr. Res. 1994;14(1):9–14
  80. Sasaki T, Matsushita M, Nanko S, Fukuda R, Kennedy JL, Tokunaga K. Schizophrenia and the HLA-DRB1 gene in the Japanese population. Am. J. Psychiatry. 1999;156(5):771–773
  81. Schlosstein L, Terasaki PI, Bluestone R, Pearson GM. High association for an HLA antigen W27 with ankylosing spondylitis. New Engl. J. Med. 1973;288:704–706
  82. Schumacher TNM, de Bruijin MLH, Vernie LN, Kast Wm, Melie CJM, Neefjes JJ, et al. Peptide selection by MHC Class I molecules. Nature. 1991;350:703–706
  83. Schwab SG, Albus M, Hallmayer J, et al.  Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint sib-pair linkage analysis. Nat. Genet. 1995;11:325–327
  84. Sette A, Buus S, Colon S, et al.  Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. Nature. 1987;328:395–397
  85. Singer L, Mayer S, Tongio MM, et al.  Etude de la frequence des antigenes HLA-A B C et Bf chez des schizophrenes d'origine alsacienne. Encephale. 1982;8:9–15
  86. Smeraldi E, Bellodi L, Cazzullo CL. Further studies on the major histocompatibility complex as a genetic marker for schizophrenia. Biol. Psychiatry. 1976;11:655–671
  87. Smeraldi E, Bellodi L, Scorza-Smeraldi R, Fabio G, Sacchetti E. HLA SD antigens and schizophrenia statistical and gentical considerations. Tissue Antigens. 1976;8:191–196
  88. Snell GD. The H2 locus of the mouse: observations and speculations concerning its comparative genetics and its polymorphism. Fol. Biol. 1968;14:335–358
  89. So A. Genetics, polymorphism and regulation of expression of HLA region. In:  Lechler R editors. HLA and Disease. London: Academic Press; 1994;p. 1–34
  90. Spitzer L, Endicott J, Robins E. Research diagnostic criteria , instrument number 58. New York: New York State psychiatric institute; 1885;
  91. Stastny P, Ball EJ, Khan MA, Olsen NP, Pincus T, Gao X. HLA-DR4 and other genetic markers in rheumatoid arthritis. Br. J. Rheumatol. 1988;27(Suppl. 2):132–138
  92. Straub RE, et al.  A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity. Nat. Genet. 1995;11:287–292
  93. Straub RE, MacLean CJ, Kendler KS. The putative schizophrenia locus on chromosome 6p: a brief overview of the linkage studies. Mol. Psychiatry. 1996;1(2):89–92
  94. Svejgaard A, Hauge M, Jersild C, et al.  The HLA system. An introductory survey. Monogr. Human Genet. 1975;7:1–100
  95. Vieira ML, Caillat-Zucman S, Gajdos P, Cohen-Kaminsky S, Casteur A, Bach JF. Identification by genomic typing of non-DR3 HLA Class II genes associated with myasthenia gravis. J. Neuroimmunol. 1993;47:115–122
  96. Wang S. Evidence for a susceptibility locus for schizophrenia on chromosome 6pter-p22. Nat. Genet. 1995;10:41–46
  97. WHO. Manual of the international classification of diseases, injuries aand causes of death. 9th revision. Geneva: WHO; 1978;
  98. Wilson AG, Duff GW. Genetic traits in common diseases. Br. Med. J. 1995;310:1482–1483
  99. Wright P, Dawson E, Donaldson PT, Underhill JA, Sham PC, Gill M, et al. Evidence from a transmission/disequilibrium study that alleles of the DRB1∗04 gene on chromosome 6p21.3 may protect against schizophrenia. Schizophr. Res. 1997;24(1,2):50–51
  100. Wright P, Donaldson PT, Curtis VA, Underhill JA, Doherty DG, Murray RM. Immunogenetic markers in schizophrenia: HLA A9 revisited. Schizophr. Res. 1995;15(1,2):50
  101. Wright P, Donaldson PT, Underhill JA, Choudhuri K, Doherty DG, Murray RM. Evidence for a resistance locus for schizophrenia close to the HLA DQA1 and DRB1 gene loci on chromosome 6p21.3. Schizophr. Res. 1997;24(1,2):50–51
  102. Wright P, Donaldson PT, Underhill JA, Doherty DG, Choudhuri K, Murray RM. Genetic association of the HLA DRB1 gene locus on chromosome 6p21.3 with schizophrenia. Am. J. Psychiatry. 1996;153:1530–1533
  103. Wright P, Gill M, Murray RM. Schizophrenia: genetics and the maternal immune response to viral infection. Am. J. Med. Genet. 1993;48:40–46
  104. Wright P, Sham PC, Gilvarry CM, Jones P, Cannon M, Sharma T, et al. Autoimmune disorders in the first degree relatives of schizophrenic and control subjects. Schizophr. Res. 1996;20:261–267
  105. Wright P, Dawson E, Donaldson PT, Undehill JA, Sham PC, Zhao J, et al. A transmission/disequilibrium study of the DRB1*04 gene locus on chromosome 9p21.3 with schizophrenia.. Schizophr. Res. 1998;32(2):75–80
  106. Zamani MG, DeHert M, Spaepen M, Hermans M, Marynen P, Cassiman JJ, et al. Study of the possible association of HLA Class II CD4 and CD3 polymorphisms with schizophrenia. Am. J. Med. Genet. Neuropsychiatr. Genet. 1994;54:372–377

PII: S0920-9964(00)00022-0

Schizophrenia Research
Volume 47, Issue 1 , Pages 1-12 , 15 January 2001

Article Tools