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ORIGINAL ARTICLE

Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia?

Jung Jin Kim Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA; Department of Psychiatry, The Catholic University of Korea, College of Medicine, Seoul, Korea

Brian H. Shirts Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA; Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania, USA

Madhulika Dayal Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA

Silviu‐alin Bacanu Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA; Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania, USA

Joel Wood Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA

Weiting Xie Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA

Xiaohua Zhang Department of Statistics, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA (now at Merck Research Laboratories, West Point, Pennsylvania, USA; currently Merck Research Laboratory, NJ, USA)

Kodavali V. Chowdari Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA

Robert Yolken Stanley Laboratory of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Bernie Devlin Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA; Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania, USA

Vishwajit L. Nimgaonkar Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA; Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania, USA

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Abstract

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.

Aim. 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.

Keywords

Acknowledgements

Funded in part by grants from the Stanley Medical Research Institute (RHY) and NIH (#MH01489, MH56242 and MH53459 to VLN; MH57881 to BD). We thank Ms Bogdana Krivogorsky for technical assistance and Ms Ann Cusic for data‐entry assistance.

Notes

Supplementary data are available on our website (http://www.pitt.edu/˜nimga/research/mhc/data/).

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Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia?

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Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia?

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