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Mol Psych:全基因组测序揭示精神分裂症发生的新位点

来源:生物谷 2013-03-10 23:09

2013年3月11日 讯 /生物谷BIOON/ --近日,刊登在国际杂志Molecular Psychiatry上的一篇研究报告中,来自丹麦阿尔胡斯大学的研究者通过研究揭示了,病毒和基因可以以某种方式相互作用,从而增加个体患精神分裂症的风险,研究者已经在发育中的胎儿中发现了这种现象。

在这项研究中,研究者首次对成千上万个病人以及健康个体进行了全基因组的完全扫描,旨在发现是否在巨细胞病毒和某些基因之间会发生相互作用,以及是否这种相互作用会影响个体患精神分裂症的风险。

感染巨细胞病毒的女性中大约有70%的女性,其所生小孩儿如果携带有巨细胞病毒某些基因突变体的话,这些小孩儿患精神分裂症的风险也会明显增加。这种病毒的突变体在15%的小孩儿中可以发现,而且其患精神分裂症的风险是一般小孩的5倍。

感染巨细胞病毒的人通常都不知道自己感染了病毒,这种病毒属于疱疹病毒家族,通常非常温和。研究者表示,即使许多风险因子在母亲和孩子体内都存在,但是也不必惊慌;或许也会存在一些其它的因子在儿童期就一直病毒的发生。精神分裂症在全世界范围内影响着1%的人群的健康,因此这项研究具有非常重要的意义。

研究者Anders Borglum说,从长远角度来讲,一种抵御巨细胞病毒的有效疫苗的开发会帮助我们预防多种形式的精神分裂症的发生。我们的研究发现也强调了,如精神分裂症一样的精神障碍,或许可以通过基因和生物环境因子的相互作用来增加其发生率及发生风险。(生物谷Bioon.com)

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

A D Børglum1,2,3, D Demontis1,3, J Grove1,3,4, J Pallesen1,3, M V Hollegaard5, C B Pedersen3,6, A Hedemand1,3, M Mattheisen7,8,9, GROUP investigators, A Uitterlinden11, M Nyegaard1,3, T Ørntoft12, C Wiuf4,13, M Didriksen14, M Nordentoft3,15, M M Nöthen7,16,17, M Rietschel18, R A Ophoff19, S Cichon7,16,20, R H Yolken21, D M Hougaard5, P B Mortensen3,6 and O Mors2,3

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10−6) and rs8057927 in CDH13 (P=1.39 × 10−5). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10−7). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10−7). This signal was replicated in the follow-up analysis (P=2.3 × 10−2). Significant interaction with maternal CMV infection was found for rs7902091 (PSNP × CMV=7.3 × 10−7) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies.

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