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

作者：Adriana Lori, Dimitrios Avramopoulos, Alex W. Wang, Jennifer G. Mullé, Nicholas Massa, Erica Duncan, Abigail Powers, Karen N. Conneely, Charles F. Gillespie, Tanja Jovanović, Kerry J. Ressler, Brad D. Pearce · 发表于：Comprehensive Psychiatry · 年份：2021 · DOI：10.1016/j.comppsych.2021.152236 · 被引用次数：7 · 研究领域：Toxoplasma gondii Research Studies、HIV Research and Treatment、RNA modifications and cancer

Schizophrenia (SCZ) is an etiologically heterogeneous disease with genetic and environmental risk factors (e.g., Toxoplasma gondii infection) differing among affected individuals. Distinguishing such risk factors may point to differences in pathophysiological pathways and facilitate the discovery of individualized treatments. Toxoplasma gondii (TOXO) has been implicated in increasing the risk of schizophrenia. To determine whether TOXO-positive individuals with SCZ have a different polygenic risk burden than uninfected people, we applied the SCZ polygenic risk score (SCZ-PRS) derived from the Psychiatric GWAS Consortium separately to the TOXO-positive and TOXO-negative subjects with the diagnosis of SCZ as the outcome variable. The SCZ-PRS does not include variants in the major histocompatibility complex. Of 790 subjects assessed for TOXO, the 662 TOXO-negative subjects (50.8% with SCZ) reached a Bonferroni corrected significant association (p = 0.00017, R2 = 0.023). In contrast, the 128 TOXO-positive individuals (53.1% with SCZ) showed no significant association (p = 0.354) for SCZ-PRS and had a much lower R2 (R2 = 0.007). To account for Type-2 error in the TOXO-positive dataset, we performed a random sampling of the TOXO-negative subpopulation (n = 130, repeated 100 times) to simulate equivalent power between groups: the p-value was <0.05 for SCZ-PRS 55% of the time but was rarely (6% of the time) comparable to the high p-value of the seropositive group at p > 0.354. We fou...