Interaction Effects of Season of Birth and Cytokine Genes onSchizotypal Traits in the General Population

Literature suggests that the effect of winter birth on vulnerability to schizophrenia might be mediated by increased expression ofproinflammatory cytokines due to prenatal infection and its inadequate regulation by anti-inflammatory factors. As the response ofthe immune system depends on genotype, this study assessed the interaction effects of cytokine genes and season of birth (SOB) onschizotypy measured with the Schizotypal Personality Questionnaire (SPQ-74). We searched for associations ofIL1Brs16944,IL4rs2243250, andIL-1RNVNTR polymorphisms, SOB, and their interactions with the SPQ-74 total score in a sample of 278 healthyindividuals. A significant effect of theIL4X SOB interaction was found,𝑝=0.007and𝜂2=0.028. We confirmed this effect using anextended sample of 373 individuals. Homozygotes CC born in winter showed the highest SPQ total score and differed significantlyfrom winter-born T allele carriers,𝑝=0.049. This difference was demonstrated for cognitive-perceptual and disorganized butnot interpersonal dimensions. The findings are consistent with the hypothesis that the cytokine genes by SOB interaction caninfluence variability of schizotypal traits in the general population. TheIL4T allele appeared to have a protective effect against thedevelopment of positive and disorganized schizotypal traits in winter-born individuals