精神分裂癥是困擾人類的重大精神疾病之一，且具有非常高的遺傳力,。近年來,，隨著全基因組關(guān)聯(lián)性分析（Genome-wide association study, GWAS）的逐步開展，人們已經(jīng)報(bào)道了一系列的精神分裂癥易感基因。然而,，這些研究大多集中在歐洲人群,，所報(bào)道的易感基因在亞洲人群中是否也與精神分裂癥顯著相關(guān)并不清楚。
昆明動(dòng)物研究所宿兵研究員的實(shí)驗(yàn)室（博士研究生李明）通過與新加坡基因組研究所和日本藤田保健衛(wèi)生大學(xué)合作,，并結(jié)合本實(shí)驗(yàn)室已采集的來自云南玉溪和昆明的樣本,，對(duì)6565份亞洲病例-對(duì)照樣本進(jìn)行了分析，目的基因?yàn)榍捌跉W洲人群中發(fā)現(xiàn)的與精神分裂癥顯著相關(guān)的基因（VRK2 rs2312147等）,。分析結(jié)果發(fā)現(xiàn),，rs2312147在亞洲人群中也與精神分裂癥強(qiáng)烈相關(guān),。隨后,，他們又增加了來自美國(guó)國(guó)立精神衛(wèi)生研究院等的歐洲人群的病例-對(duì)照樣本，并發(fā)現(xiàn)相關(guān)性增強(qiáng),。這些證據(jù)很好地支持了前期GWAS的發(fā)現(xiàn),。同時(shí)，他們發(fā)現(xiàn)VRK2在精神分裂癥患者血液中mRNA表達(dá)相對(duì)正常人明顯升高,，進(jìn)一步支持了相關(guān)性分析的結(jié)果,。利用核磁共振影像學(xué)分析，在286個(gè)漢族健康個(gè)體中,，他們分析了rs2312147與腦結(jié)構(gòu)（全腦容量等）的關(guān)系,，并發(fā)現(xiàn)rs2312147與全腦容量以及全腦白質(zhì)體積顯著相關(guān)，暗示VRK2可能在大腦發(fā)育中起作用,。該研究證實(shí)了VRK2在中國(guó)人群中也是精神分裂癥易感基因,，結(jié)果發(fā)表于精神分裂癥國(guó)際核心期刊《Schizophrenia Research》.（生物谷Bioon.com）
doi: 10.1016/j.schres.2012.10.008
PMC:
PMID:
Meta-analysis and brain imaging data support the involvement of VRK2 (rs2312147) in schizophrenia susceptibility
Li M, Wang Y, Zheng XB, Ikeda M, Iwata N, Luo XJ, Chong SA, Lee J, Rietschel M, Zhang F, Müller-Myhsok B, Cichon S, Weinberger DR, Mattheisen M, Schulze TG, Martin NG, Mitchell PB, Schofield PR, Liu JJ, Su B; MooDS Consortium.
Recent genome-wide association studies have reported a set of schizophrenia susceptibility genes, but many of them await further replications in additional samples. Here we analyzed 5 genome-wide supported variants in a Han Chinese sample, and the variant rs2312147 at VRK2 showed significant association, which was confirmed in the meta-analysis combining multiple Asian and European samples (P=3.17×10(-4), N=7498). Rs2312147 is also associated with brain structure in healthy subjects, including the total brain volume and the white matter volume. Gene expression analyses indicated an up-regulation of VRK2 in schizophrenia patients. Our data provide further evidence for the contribution of VRK2 to schizophrenia.
