Infection and inflammation in schizophrenia and bipolar disorder

A genome wide study for interactions with genetic variation

Dimitrios Avramopoulos, Brad D. Pearce, John McGrath, Paula Wolyniec, Ruihua Wang, Nicole Eckart, Alexandros Hatzimanolis, Fernando S Goes, Gerald Nestadt, Jennifer Mulle, Karen Coneely, Myfanwy Hopkins, Ingo Ruczinski, Robert H Yolken, Ann E Pulver

Research output: Contribution to journalArticle

Abstract

Inflammation and maternal or fetal infections have been suggested as risk factors for schizophrenia (SZ) and bipolar disorder (BP). It is likely that such environmental effects are contingent on genetic background. Here, in a genome-wide approach, we test the hypothesis that such exposures increase the risk for SZ and BP and that the increase is dependent on genetic variants. We use genome-wide genotype data, plasma IgG antibody measurements against Toxoplasma gondii, Herpes simplex virus type 1, Cytomegalovirus, Human Herpes Virus 6 and the food antigen gliadin as well as measurements of C-reactive protein (CRP), a peripheral marker of inflammation. The subjects are SZ cases, BP cases, parents of cases and screened controls. We look for higher levels of our immunity/infection variables and interactions between them and common genetic variation genome-wide. We find many of the antibody measurements higher in both disorders. While individual tests do not withstand correction for multiple comparisons, the number of nominally significant tests and the comparisons showing the expected direction are in significant excess (permutation p=0.019 and 0.004 respectively). We also find CRP levels highly elevated in SZ, BP and the mothers of BP cases, in agreement with existing literature, but possibly confounded by our inability to correct for smoking or body mass index. In our genome-wide interaction analysis no signal reached genome-wide significance, yet many plausible candidate genes emerged. In a hypothesis driven test, we found multiple interactions among SZ-associated SNPs in the HLA region on chromosome 6 and replicated an interaction between CMV infection and genotypes near the CTNNA3 gene reported by a recent GWAS. Our results support that inflammatory processes and infection may modify the risk for psychosis and suggest that the genotype at SZ-associated HLA loci modifies the effect of these variables on the risk to develop SZ.

Original languageEnglish (US)
Article numbere0116696
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 17 2015

Fingerprint

Bipolar Disorder
Schizophrenia
Genes
inflammation
Genome
Inflammation
genetic variation
genome
Infection
infection
C-reactive protein
Genotype
Viruses
C-Reactive Protein
genotype
testing
Human herpesvirus 5
Human herpesvirus 1
Gliadin
Chromosomes, Human, Pair 6

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Infection and inflammation in schizophrenia and bipolar disorder : A genome wide study for interactions with genetic variation. / Avramopoulos, Dimitrios; Pearce, Brad D.; McGrath, John; Wolyniec, Paula; Wang, Ruihua; Eckart, Nicole; Hatzimanolis, Alexandros; Goes, Fernando S; Nestadt, Gerald; Mulle, Jennifer; Coneely, Karen; Hopkins, Myfanwy; Ruczinski, Ingo; Yolken, Robert H; Pulver, Ann E.

In: PLoS One, Vol. 10, No. 3, e0116696, 17.03.2015.

Research output: Contribution to journalArticle

Avramopoulos, Dimitrios ; Pearce, Brad D. ; McGrath, John ; Wolyniec, Paula ; Wang, Ruihua ; Eckart, Nicole ; Hatzimanolis, Alexandros ; Goes, Fernando S ; Nestadt, Gerald ; Mulle, Jennifer ; Coneely, Karen ; Hopkins, Myfanwy ; Ruczinski, Ingo ; Yolken, Robert H ; Pulver, Ann E. / Infection and inflammation in schizophrenia and bipolar disorder : A genome wide study for interactions with genetic variation. In: PLoS One. 2015 ; Vol. 10, No. 3.
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AU - Wang, Ruihua

AU - Eckart, Nicole

AU - Hatzimanolis, Alexandros

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AU - Nestadt, Gerald

AU - Mulle, Jennifer

AU - Coneely, Karen

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