Li Xiao, Zhang Wen, Zhang Chen, Yi Zhenghui, Zhang Deng-Feng, Gong Wei, Tang Jinsong, Wang Dong, Lu Weihong, Chen Xiaogang, Fang Yiru, Yao Yong-Gang
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China.
Mol Genet Genomics. 2015 Apr;290(2):585-92. doi: 10.1007/s00438-014-0942-1. Epub 2014 Oct 30.
Schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples (P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia.
精神分裂症是一种病因复杂的常见精神疾病。线粒体功能障碍在精神分裂症中经常被报道。磷酸酶和张力同源物诱导激酶1（PINK1）和早老素相关类菱形蛋白酶（PARL）是线粒体蛋白，这两个基因的遗传变异可能通过影响线粒体功能而赋予精神分裂症遗传易感性。在本研究中，我们进行了一项两阶段基因关联研究来验证这一假设。我们对4个PINK1和5个PARL基因变异进行基因分型，并在两个独立的包含2510名汉族个体的病例对照队列中评估这9个单核苷酸多态性（SNP）与精神分裂症的潜在关联。在经Bonferroni校正后，我们的样本中未发现PINK1和PARL基因的常见遗传变异与精神分裂症有正相关。对最新更新的精神病遗传学联盟（PGC）数据集的重新分析证实了我们的阴性结果。有趣的是，根据表达数量性状位点（eQTL）分析，一个仅在湖南样本中显示出边缘显著关联（P = 0.032）的PINK1 SNP（rs10916832）与精神分裂症易感基因KIF17的表达相关。我们的研究表明，PINK1和PARL基因的常见遗传变异不太可能参与精神分裂症的发病。进一步的研究对于明确PINK1和PARL基因在精神分裂症中的作用至关重要。
