Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

Toxoplasma gondii, is implicated in schizophrenia and related disorders, but also in Alzheimer’s or Parkinson’s disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. The susceptibility genes for multiple sclerosis > Alzheimer’s disease > schizophrenia > bipolar disorder> depression > childhood obesity > Parkinson’s disease > attention deficit hyperactivity disorder (P from 8.01E-05 (ADHD) to 1.22E-71 (multiple sclerosis), and autism (p=0.013), but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD) to 33% (Multiple Sclerosis) of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively) to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity) and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as) to the disease itself.

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