Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure

Mikhil Bamne, Joel Wood, Kodavali Chowdari, Annie M. Watson, Cemil Celik, Hader Mansour, Lambertus Klei, Ruben C. Gur, L. Dianne Bradford, Monica E. Calkins, Alberto Santos, Neil Edwards, Joseph Kwentus, Joseph Patrick McEvoy, Trina B. Allen, Robert M. Savage, Henry A. Nasrallah, Raquel E. Gur, Rodney T. Perry, Rodney C.P. GoBernie Devlin, Robert Yolken, Vishwajit L. Nimgaonkar

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Genome-wide association studies (GWAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors for schizophrenia (SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. Method: GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1), cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific antibody assays. Results: Five SNPs were nominally associated with SZ, adjusted for population admixture (P <. 05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. Conclusions: We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples.

Original languageEnglish (US)
Pages (from-to)1149-1154
Number of pages6
JournalSchizophrenia Bulletin
Volume38
Issue number6
DOIs
StatePublished - Nov 1 2012

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HLA Antigens
Single Nucleotide Polymorphism
Schizophrenia
Genome-Wide Association Study
Human Herpesvirus 1
African Americans
Chromosomes
Alleles
Toxoplasma
Cytomegalovirus
Multivariate Analysis
Genotype
Antibodies
Population

Keywords

  • African American
  • HLA
  • HSV-1
  • cytomegalovirus
  • gene
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Bamne, M., Wood, J., Chowdari, K., Watson, A. M., Celik, C., Mansour, H., ... Nimgaonkar, V. L. (2012). Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure. Schizophrenia Bulletin, 38(6), 1149-1154. https://doi.org/10.1093/schbul/sbs087

Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure. / Bamne, Mikhil; Wood, Joel; Chowdari, Kodavali; Watson, Annie M.; Celik, Cemil; Mansour, Hader; Klei, Lambertus; Gur, Ruben C.; Bradford, L. Dianne; Calkins, Monica E.; Santos, Alberto; Edwards, Neil; Kwentus, Joseph; McEvoy, Joseph Patrick; Allen, Trina B.; Savage, Robert M.; Nasrallah, Henry A.; Gur, Raquel E.; Perry, Rodney T.; Go, Rodney C.P.; Devlin, Bernie; Yolken, Robert; Nimgaonkar, Vishwajit L.

In: Schizophrenia Bulletin, Vol. 38, No. 6, 01.11.2012, p. 1149-1154.

Research output: Contribution to journalArticle

Bamne, M, Wood, J, Chowdari, K, Watson, AM, Celik, C, Mansour, H, Klei, L, Gur, RC, Bradford, LD, Calkins, ME, Santos, A, Edwards, N, Kwentus, J, McEvoy, JP, Allen, TB, Savage, RM, Nasrallah, HA, Gur, RE, Perry, RT, Go, RCP, Devlin, B, Yolken, R & Nimgaonkar, VL 2012, 'Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure', Schizophrenia Bulletin, vol. 38, no. 6, pp. 1149-1154. https://doi.org/10.1093/schbul/sbs087
Bamne, Mikhil ; Wood, Joel ; Chowdari, Kodavali ; Watson, Annie M. ; Celik, Cemil ; Mansour, Hader ; Klei, Lambertus ; Gur, Ruben C. ; Bradford, L. Dianne ; Calkins, Monica E. ; Santos, Alberto ; Edwards, Neil ; Kwentus, Joseph ; McEvoy, Joseph Patrick ; Allen, Trina B. ; Savage, Robert M. ; Nasrallah, Henry A. ; Gur, Raquel E. ; Perry, Rodney T. ; Go, Rodney C.P. ; Devlin, Bernie ; Yolken, Robert ; Nimgaonkar, Vishwajit L. / Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure. In: Schizophrenia Bulletin. 2012 ; Vol. 38, No. 6. pp. 1149-1154.
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abstract = "Background: Genome-wide association studies (GWAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors for schizophrenia (SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. Method: GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1), cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific antibody assays. Results: Five SNPs were nominally associated with SZ, adjusted for population admixture (P <. 05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. Conclusions: We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples.",
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AU - Bamne, Mikhil

AU - Wood, Joel

AU - Chowdari, Kodavali

AU - Watson, Annie M.

AU - Celik, Cemil

AU - Mansour, Hader

AU - Klei, Lambertus

AU - Gur, Ruben C.

AU - Bradford, L. Dianne

AU - Calkins, Monica E.

AU - Santos, Alberto

AU - Edwards, Neil

AU - Kwentus, Joseph

AU - McEvoy, Joseph Patrick

AU - Allen, Trina B.

AU - Savage, Robert M.

AU - Nasrallah, Henry A.

AU - Gur, Raquel E.

AU - Perry, Rodney T.

AU - Go, Rodney C.P.

AU - Devlin, Bernie

AU - Yolken, Robert

AU - Nimgaonkar, Vishwajit L.

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N2 - Background: Genome-wide association studies (GWAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors for schizophrenia (SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. Method: GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1), cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific antibody assays. Results: Five SNPs were nominally associated with SZ, adjusted for population admixture (P <. 05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. Conclusions: We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples.

AB - Background: Genome-wide association studies (GWAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors for schizophrenia (SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. Method: GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1), cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific antibody assays. Results: Five SNPs were nominally associated with SZ, adjusted for population admixture (P <. 05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. Conclusions: We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples.

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KW - gene

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