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A few studies suggested the contribution of PPARs to the etiology of schizophrenia (SCZ). However, it is still not clear whether PPAR genes have a direct association with SCZ. The potential linkage between SCZ and the variants within PPAR encoding genes (PPARA, PPARD, and PPARG) was tested in a large cohort Genome-wide association study (GWAS) study. Then a mega-analysis was conducted using 14 gene expression profiling experiments in various human brain regions. Finally, the expression levels of the three PPAR-encoding genes were quantified in early-onset SCZ patients. Only one PPARG polymorphisms, rs62242085, presented a minor frequency deviation in the SCZ cohort (p-value= 0.035). None of the PPARs presented significant expression change within the brain regions represented by 14 datasets acquired from different populations (p-value>0.14) nor in the whole blood of early-onset overall SCZ patients (p-value>0.22). However, compared to healthy female controls, female, early-onset SCZ patients presented a moderate but significant decrease in the expression level of PPARD (LFC=-0.55; p-value=0.02) and a strong, but non-significant decrease in expression of PPARG(LFC=-1.30; p-value=0.13). Our results do not support a significant association between variants in PPAR-encoding genes and SCZ overall but suggest a necessity to explore the role of PPARD and PPARG in SCZ phenotypes, specifically in females.

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