Department of Psychiatry, First Hospital /First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
Department of Biomedical Engineering, Tianjin University, Tianjin, China.
Biosci Rep. 2020 Jul 31;40(7). doi: 10.1042/BSR20201083.
A few studies suggested the contribution of PPARs to the etiology of schizophrenia (SCZ). However, it is still not clear whether variants in PPAR-encoding 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). 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 PPAR-encoding genes presented significant expression change within the brain regions profiled in 14 datasets acquired from different populations (P-value > 0.14) or in the whole blood of early-onset overall SCZ patients (P-value > 0.22). However, compared with 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, but suggest a necessity to explore the role of PPARD and PPARG in early SCZ phenotypes, specifically in females.
一些研究表明过氧化物酶体增殖物激活受体（PPARs）对精神分裂症（SCZ）的病因有一定的贡献。然而，PPAR 编码基因中的变体是否与 SCZ 有直接关联尚不清楚。在一项大规模的全基因组关联研究（GWAS）中，研究人员测试了 SCZ 与 PPAR 编码基因（PPARA、PPARD 和 PPARG）内变体之间的潜在联系。然后，使用来自不同人群的 14 个不同大脑区域的基因表达谱实验进行了 mega 分析。最后，在发病早的 SCZ 患者中定量检测了这三个 PPAR 编码基因的表达水平。只有一个 PPARG 多态性 rs62242085 在 SCZ 队列中表现出较小的频率偏差（P 值=0.035）。在从不同人群获得的 14 个数据集所分析的大脑区域内，没有一个 PPAR 编码基因表现出显著的表达变化（P 值>0.14），也没有在发病早的总体 SCZ 患者的全血中表现出显著的表达变化（P 值>0.22）。然而，与健康女性对照相比，发病早的女性 SCZ 患者的 PPARD 表达水平明显降低（LFC=-0.55；P 值=0.02），而 PPARG 的表达水平虽然较强，但无统计学意义降低（LFC=-1.30；P 值=0.13）。我们的研究结果不支持 PPAR 编码基因中的变体与 SCZ 之间存在显著关联，但表明有必要探索 PPARD 和 PPARG 在早期 SCZ 表型中的作用，特别是在女性中。
