title: Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA.
authors.forename: Mikhil
authors.initials: M
authors.lastname: Bamne
authors.forename: Joel
authors.initials: J
authors.lastname: Wood
authors.forename: Kodavali
authors.initials: K
authors.lastname: Chowdari
authors.forename: Annie M
authors.initials: AM
authors.lastname: Watson
authors.forename: Cemil
authors.initials: C
authors.lastname: Celik
authors.forename: Hader
authors.initials: H
authors.lastname: Mansour
authors.forename: Lambertus
authors.initials: L
authors.lastname: Klei
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.forename: L DiAnne
authors.initials: LD
authors.lastname: Bradford
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.forename: Alberto B
authors.initials: AB
authors.lastname: Santos
authors.forename: Neil
authors.initials: N
authors.lastname: Edwards
authors.forename: Joseph
authors.initials: J
authors.lastname: Kwentus
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Trina B
authors.initials: TB
authors.lastname: Allen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Savage
authors.forename: Henry A
authors.initials: HA
authors.lastname: Nasrallah
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.forename: Rodney T
authors.initials: RT
authors.lastname: Perry
authors.forename: Rodney C P
authors.initials: RC
authors.lastname: Go
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000523:psychology; D000071797:Butyrophilins; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006561:Herpes Simplex / Q000150:complications; D018259:Herpesvirus 1, Human; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000469:parasitology / Q000821:virology; D016781:Toxoplasmosis, Cerebral / Q000150:complications
chemical_list: C576586:BTN3A2 protein, human; D000071797:Butyrophilins; D006680:HLA Antigens; D008565:Membrane Proteins