Impact of a microRNA MIR137 Susceptibility Variant on Brain Function in People at High Genetic Risk of Schizophrenia or Bipolar Disorder
Impact of a microRNA MIR137 Susceptibility Variant on Brain Function in People at High Genetic Risk of Schizophrenia or Bipolar Disorder
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DOI：
10.1038/npp.2012.137
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发表时间：
2012-11-01
影响因子：
7.6
通讯作者：
McIntosh, Andrew M.
中科院分区：
文献类型：
--
作者：
Whalley, Heather C.;Papmeyer, Martina;McIntosh, Andrew M.
最近的一项“大型分析”结合了来自4万多个个体的全基因组关联研究数据，在全基因组显著水平上发现了与精神分裂症（SCZ）相关的新遗传位点。最强的发现是microRNA MIR137的一个假定的初级转录物的内含子内的一个位点。在当前的研究中，我们研究了该基因座（rs1625579, G/T，其中T是常见的和假定的风险等位基因）的变异对句子完成任务中大脑激活的影响，以区分SCZ、双相情感障碍（BD）及其亲属与对照组。为了检验rs1625579基因型会影响大脑激活的假设，我们研究了三组执行句子补全范式的个体：(i) SCZ高遗传风险个体（n = 44）， （ii） BD高遗传风险个体（n = 90），以及（iii）健康对照（n = 81）。GT和GG个体的基因型组为“RISK -”，TT纯合子的基因型组为“RISK +”。基因型的主要影响是风险个体右后内侧额回ba6的激活显著增加。左侧杏仁核和左侧中央前/后回也存在显著的基因型*组相互作用。这是由于对照组（具有风险-基因型的个体比具有风险+基因型的个体表现出更大的激活）和SCZ高危组之间的差异，在SCZ高危组中，基因型效应相反。这些结果表明，新发现的SCZ位点可能以某种方式影响大脑激活，这种方式部分依赖于SCZ现有遗传易感性的存在。神经精神药理学（2012）37,2720-2729；doi: 10.1038 / npp.2012.137;2012年8月1日在线发布
A recent 'mega-analysis' combining genome-wide association study data from over 40 000 individuals identified novel genetic loci associated with schizophrenia (SCZ) at genome-wide significance level. The strongest finding was a locus within an intron of a putative primary transcript for microRNA MIR137. In the current study, we examine the impact of variation at this locus (rs1625579, G/T; where T is the common and presumed risk allele) on brain activation during a sentence completion task that differentiates individuals with SCZ, bipolar disorder (BD), and their relatives from controls. We examined three groups of individuals performing a sentence completion paradigm: (i) individuals at high genetic risk of SCZ (n = 44), (ii) individuals at high genetic risk of BD (n = 90), and (iii) healthy controls (n = 81) in order to test the hypothesis that genotype at rs1625579 would influence brain activation. Genotype groups were assigned as 'RISK -' for GT and GG individuals, and 'RISK +' for TT homozygotes. The main effect of genotype was significantly greater activation in the RISK - individuals in the posterior right medial frontal gyrus, BA 6. There was also a significant genotype*group interaction in the left amygdala and left pre/postcentral gyrus. This was due to differences between the controls (where individuals with the RISK - genotype showed greater activation than RISK + subjects) and the SCZ high-risk group, where the opposite genotype effect was seen. These results suggest that the newly identified SCZ locus may influence brain activation in a manner that is partly dependent on the presence of existing genetic susceptibility for SCZ. Neuropsychopharmacology (2012) 37, 2720-2729; doi:10.1038/npp.2012.137; published online 1 August 2012