Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia?
BACKGROUND
Published data support genetic variants, as well as certain infectious agents, as potential risk factors for schizophrenia. Less is known about interactions between the risk factors.


OBJECTIVE
To evaluate exposure to infectious agents and host genetic variation as joint risk factors.


METHODS
We investigated four infectious agents: cytomegalovirus (CMV), herpes simplex viruses 1 and 2 (HSV1, HSV2), and Toxoplasma gondii (TOX). We initially compared exposure using specific serum antibodies, among simplex and multiplex nuclear families (one or more than one affected offspring, respectively). If interactions between infectious agents and host genetic variation are important risk factors for schizophrenia, we reasoned that they would be more prominent among multiplex versus simplex families. We also evaluated the role of variation at chromosome 6p21-p23 in conjunction with exposure. We used 22 short tandem repeat polymorphisms (STRPs) dispersed across this region.


RESULTS
Though exposure to all four agents was increased among multiplex families versus simplex families, the difference was consistently significant only for CMV (odds of exposure to CMV in multiplex families: 2.47, 95% CI: 1.48-5.33). Transmission disequilibrium tests and case-control comparisons using STRPs revealed significant linkage/association with D6S2672 among CMV+ schizophrenia patients.


CONCLUSIONS
Polymorphisms near D6S2672 could confer risk for schizophrenia in conjunction with CMV exposure.
Kim
Jung Jin
JJ
Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania 15213, USA.
Shirts
Brian H
BH
Dayal
Madhulika
M
Bacanu
Silviu-Alin
SA
Wood
Joel
J
Xie
Weiting
W
Zhang
Xiaohua
X
Chowdari
Kodavali V
KV
Yolken
Robert
R
Devlin
Bernie
B
Nimgaonkar
Vishwajit L
VL
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology*; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics; D018259:Herpesvirus 1, Human; D018258:Herpesvirus 2, Human; D006801:Humans; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000276:immunology*; D014122:Toxoplasma
D000914:Antibodies, Viral; D006680:HLA Antigens