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首页> 美国卫生研究院文献>Annals of Translational Medicine >AB166. Replicative genetic association analysis reveals genetic markers of schizophrenia and Alzheimer’s disease in Russians and Kazakhs and demonstrates overlapping associations pattern between two diseases
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AB166. Replicative genetic association analysis reveals genetic markers of schizophrenia and Alzheimer’s disease in Russians and Kazakhs and demonstrates overlapping associations pattern between two diseases

机译：AB166。复制遗传关联分析揭示了俄罗斯人和哈萨克人精神分裂症和阿尔茨海默氏病的遗传标记并证明了两种疾病之间的重叠关联模式

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Replicative analysis of genetic markers, previously identified in genome-wide association studies (GWAS) for neuropsychiatric diseases, in population of various origins may contribute to better understanding of genetic composition of the diseases. In this study 50 SNPs found in GWAS for schizophrenia (SZ), Alzheimer’s diseases (AD) and cognitive endophenotypes were genotyped in patients and control samples from Russian and Kazakh populations. Eight polymorphic markers (SNPs in regions of genes for APOЕ, APOJ, CSMD1, CCDC60, SNX29, PICALM, NOTCH4 and NRIP1) were associated with AD in Russian population. Associations of 10 genetic markers with SZ in Russian populations (markers in regions of genes for NRGN, KCNB2, NRIP1, CCDC60, LSM1, LOC100129100/LOC100509857, CSMD1, CPVL, POM121L2 and NDE1P1/PRMT6) and 8 genetic markers in Kazakh population (VRK2, KCNB2, CPVL, BRD1, PVRL2, ARHGAP1, CD33 u GPR89P/TRV-AAC1-5) were replicated. Multidimensional reduction methods revealed epistatic interaction of several genetic loci in formation of susceptibility to SZ in populations of various ethnic origins. Overlapping fields of genetic associations for AD and SZ, demonstrating some similarity in inherited background for both diseases, were found. This interaction may be implemented through common unknown levels in pathogenesis of AD and SZ, mediated by cognitive endophenotypes. Bioinformatic analysis of biological functions of associated genes revealed that among primary biological processes enriched by genes under study are the processes of lipid metabolism, cellular interactions, various regulatory and transport processes in neural cells, processes of immune response regulation. Substantial part of investigated genes forms an interacting network, which consisted of distinct clusters corresponding to major biological processes, were genes under study are involved, and to basic molecular functions of their products. In general, data obtained in the project, extend the understanding of genetic component in neuro-psychiatric diseases, as well as the biological processes and functions, implemented in the manifestation of genetic susceptibility to AD and SZ.
机译：以前在神经精神疾病的全基因组关联研究（GWAS）中对各种来源的人群进行的遗传标记的重复分析可能有助于更好地了解疾病的遗传组成。在这项研究中，在GWAS中针对精神分裂症（SZ），阿尔茨海默氏病（AD）和认知内表型的50个SNP在患者和来自俄罗斯和哈萨克族人群的对照样本中进行了基因分型。八个多态性标记（APOЕ，APOJ，CSMD1，CCDC60，SNX29，PICALM，NOTCH4和NRIP1的基因区域中的SNP）与俄罗斯人群的AD相关。俄罗斯人口中10个遗传标记与SZ的关联（NRGN，KCNB2，NRIP1，CCDC60，LSM1，LOC100129100 / LOC100509857，CSMD1，CPVL，POM121L2和NDE1P1 / PRMT6的基因区域中的标记）和哈萨克族（VRK2）中的8个遗传标记，KCNB2，CPVL，BRD1，PVRL2，ARHGAP1，CD33（GPR89P / TRV-AAC1-5）复制。多维还原方法揭示了在不同种族血统的人群中对SZ易感性形成中几个遗传基因座的上位相互作用。发现了AD和SZ的遗传关联的重叠域，表明两种疾病的遗传背景具有相似性。这种相互作用可以通过认知内表型介导的AD和SZ发病机理中常见的未知水平来实现。对相关基因生物学功能的生物信息学分析显示，在研究中的基因丰富的主要生物学过程中，有脂质代谢过程，细胞相互作用，神经细胞中各种调节和转运过程，免疫应答调节过程。被研究基因的实质部分形成一个相互作用的网络，该网络由与主要生物学过程相对应的不同簇组成，这些簇涉及所研究的基因及其产物的基本分子功能。通常，从该项目中获得的数据扩展了对神经精神疾病的遗传成分以及生物学过程和功能的理解，并以对AD和SZ的遗传易感性表现形式实现。

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