Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients

Lori, Adriana; Avramopoulos, Dimitrios; Wang, Alex W.; Mullé, Jennifer G.; Massa, Nicholas; Duncan, Erica; Powers, Abigail; Conneely, Karen N.; Gillespie, Charles F.; Jovanović, Tanja; Ressler, Kerry J.; Pearce, Brad D.

doi:10.1016/j.comppsych.2021.152236

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…A similar GWAS of the same Ashkenazi cohort by Lori et al. did not find evidence for a correlation between schizophrenia and positive serology for T. gondii , but did note the genetic architecture of SNPs predicting schizophrenia are fundamentally different between seropositive and sero-negative schizophrenics ( Lori et al., 2021 ). Although serological studies in humans are the most practical way to answer epidemiological questions regarding T. gondii infections ( Dard et al., 2016 ), at best its use in GWAS has yielded marginal genetic associations for schizophrenia or susceptibility to infection.…”

Section: Introductionmentioning

confidence: 95%

Forward Genetics in Apicomplexa Biology: The Host Side of the Story

Sánchez‐Arcila

Jensen

2022

Front. Cell. Infect. Microbiol.

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Forward genetic approaches have been widely used in parasitology and have proven their power to reveal the complexities of host-parasite interactions in an unbiased fashion. Many aspects of the parasite’s biology, including the identification of virulence factors, replication determinants, antibiotic resistance genes, and other factors required for parasitic life, have been discovered using such strategies. Forward genetic approaches have also been employed to understand host resistance mechanisms to parasitic infection. Here, we will introduce and review all forward genetic approaches that have been used to identify host factors involved with Apicomplexa infections, which include classical genetic screens and QTL mapping, GWAS, ENU mutagenesis, overexpression, RNAi and CRISPR-Cas9 library screens. Collectively, these screens have improved our understanding of host resistance mechanisms, immune regulation, vaccine and drug designs for Apicomplexa parasites. We will also discuss how recent advances in molecular genetics give present opportunities to further explore host-parasite relationships.

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Section: Introductionmentioning

confidence: 95%

Forward Genetics in Apicomplexa Biology: The Host Side of the Story

Sánchez‐Arcila

Jensen

2022

Front. Cell. Infect. Microbiol.

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“…In a meta-analysis of a toxoplasmosis susceptibility GWAS done by Wang et al, there was enrichment for genes associated with schizophrenia in populations with IgG seropositivity for Toxo, an indication of previous infection [ 48 ]. Although this shows that genes involved in schizophrenia development may also be involved in the susceptibility or the immune response to Toxo , conflicting evidence from a study by Lori et al showed that PRS scores (based on schizophrenia GWAS data) do not predict schizophrenia in individuals who are IgG seropositive for Toxo [ 49 ]. The immune response and neuroinflammation due to Toxo and other infectious agents have also been implicated as a potential mechanism for GxE interactions.…”

Section: Gene-environment (Gxe) Interactionsmentioning

confidence: 99%

Gene-Environment Interactions in Schizophrenia: A Literature Review

Wahbeh

Avramopoulos

2021

Genes

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Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well recognized that non-genetic factors such as certain infections, cannabis use, psychosocial stress, childhood adversity, urban environment, and immigrant status also play a role. Whenever genetic and non-genetic factors co-exist, interaction between the two is likely. This means that certain exposures would only be of consequence given a specific genetic makeup. Here, we provide a brief review of studies reporting evidence of such interactions, exploring genes and variants that moderate the effect of the environment to increase risk of developing psychosis. Discovering these interactions is crucial to our understanding of the pathogenesis of complex disorders. It can help in identifying individuals at high risk, in developing individualized treatments and prevention plans, and can influence clinical management.

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“…Latent toxoplasmosis has been associated with tissue cysts of T. gondii in the brain tissue [ 16 , 17 ]. Previous studies showed an association between T. gondii antibody seropositivity and the presence of schizophrenia [ 18 , 19 , 20 ], bipolar disease [ 21 , 22 ], suicide attempts [ 23 ], self-directed violence [ 24 ], depression [ 25 ], and alcohol abuse [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Toxoplasma gondii IgG Antibodies and Associated Risk Factors in Psychiatric Patients from Western Romania: A Cross-Sectional Study

Grada,

Mihu,

Oatis

et al. 2024

Microorganisms

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Infection with the coccidian parasite Toxoplasma gondii was associated with an increased risk of several mental disorders. We conducted a case–control study of 464 consecutive psychiatric patients and assessed the prevalence of IgG antibodies against T. gondii and the potential risk factors associated with infection. T. gondii-specific antibodies were determined using a chemiluminescence assay. A questionnaire was utilized to assess the potential correlation between risk factors and Toxoplasma gondii seropositivity. IgG antibodies were found in 325 (70.04%) of the patients. We observed a higher likelihood of positive IgG antibodies against Toxoplasma gondii in older individuals, patients residing in rural areas, and females. We also noted associations between Toxoplasma gondii infection and certain risk factors, like activities that involve contact with soil, low-income levels, and limited educational attainment. Our findings indicate a high prevalence of T. gondii infection among psychiatric patients from Western Romania and provide new information regarding the potential risk factors associated with T. gondii in this population group. This study may serve as a foundation for future research and the development of preventive strategies.

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Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients

Cited by 6 publications

References 24 publications

Forward Genetics in Apicomplexa Biology: The Host Side of the Story

Forward Genetics in Apicomplexa Biology: The Host Side of the Story

Gene-Environment Interactions in Schizophrenia: A Literature Review

Prevalence of Toxoplasma gondii IgG Antibodies and Associated Risk Factors in Psychiatric Patients from Western Romania: A Cross-Sectional Study

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