title: Common variants of the PINK1 and PARL genes do not confer genetic susceptibility to schizophrenia in Han Chinese.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Yi
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Jinsong
authors.initials: J
authors.lastname: Tang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Weihong
authors.initials: W
authors.lastname: Lu
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Chen
authors.forename: Yiru
authors.initials: Y
authors.lastname: Fang
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D016022:Case-Control Studies; D002681:China; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D015810:Linkage Disequilibrium; D045726:Metalloproteases / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000235:genetics*; D040641:Quantitative Trait Loci; D012559:Schizophrenia / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D016547:Kinesins; D045726:Metalloproteases; D024101:Mitochondrial Proteins; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C485813:KIF17 protein, human; C485223:PARL protein, human