title: Systematic association analysis of microRNA machinery genes with schizophrenia informs further study.
abstract: microRNAs (miRNAs) play a vital role in development via the post-transcriptional regulation of most genes. Variation in the miRNA machinery pathway proteins which mediate the biogenesis, maturation, transportation, and functioning of miRNAs might be relevant to human traits. In this work, we explored the role of 59 miRNA machinery genes in schizophrenia (SZ). Association analysis of 967 single nucleotide polymorphisms within these genes detected that an intronic polymorphism of EIF4ENIF1, rs7289941, was significantly associated with SZ (P=4.10E-5). We failed to replicate this result in a validation sample comprising 1027 healthy controls and 1012 SZ cases, and the combined data yielded nominal significance (P=0.013). We conducted a gene-based association analysis using VEGAS and SKAT, and found seven associated genes in total, including EIF4ENIF1, PIWIL2, and DGCR8, but none survived correction for multiple testing. Taken together, our data do not provide strong support for the association of common variants within miRNA machinery genes with SZ in the Han Chinese population, but implicate several promising candidate genes for further research.
authors.affiliation: Institute of Mental Health, Peking University, PR China. zfq@bjmu.edu.cn
authors.forename: Fuquan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Chen
authors.forename: Chenxing
authors.initials: C
authors.lastname: Liu
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ruan
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D035683:MicroRNAs