Cosgrove Donna, Mothersill David O, Whitton Laura, Harold Denise, Kelly Sinead, Holleran Laurena, Holland Jessica, Anney Richard, Richards Alex, Mantripragada Kiran, Owen Michael, O'Donovan Michael C, Gill Michael, Corvin Aiden, Morris Derek W, Donohoe Gary
The Cognitive Genetics & Cognitive Therapy Group, The School of Psychology and Discipline of Biochemistry, The Centre for Neuroimaging & Cognitive Genomics, National University of Ireland Galway, Galway, Ireland.
School of Biotechnology, Dublin City University, Dublin, Ireland.
Am J Med Genet B Neuropsychiatr Genet. 2018 Apr;177(3):369-376. doi: 10.1002/ajmg.b.32620. Epub 2018 Feb 8.
Multiple genome-wide association studies of schizophrenia have implicated genetic variants within the gene encoding microRNA-137. As risk variants within or regulated by MIR137 have been implicated in memory performance, we investigated the additive effects of schizophrenia-associated risk variants in genes empirically regulated by MIR137 on brain regions associated with memory function. A polygenic risk score (PRS) was calculated (at a p = 0.05 threshold), using this empirically regulated MIR137 gene set, to investigate associations between this PRS and structural brain measures. These measures included total brain volume, cortical thickness, cortical surface area, and hippocampal volume, in a sample of 216 individuals consisting of healthy participants (n = 171) and patients with psychosis (n = 45). We did not observe a significant association between MIR137 PRS and these cortical thickness, surface area or hippocampal volume measures linked to memory function; a significant association between increasing PRS and decreasing total brain volume, independent of diagnosis status (R = 0.008, Beta = -0.09, p = 0.029), was observed. This did not survive correction for multiple testing. In conclusion, our study yielded only suggestive evidence that risk variants interacting with MIR137 impacts on cortical structure.
多项精神分裂症全基因组关联研究表明,编码微小RNA - 137的基因内存在遗传变异。由于MIR137内或受其调控的风险变异与记忆表现有关,我们研究了MIR137实证调控基因中的精神分裂症相关风险变异对与记忆功能相关脑区的累加效应。使用这个实证调控的MIR137基因集计算多基因风险评分(PRS)(p值阈值为0.05),以研究该PRS与脑结构测量值之间的关联。这些测量值包括全脑体积、皮质厚度、皮质表面积和海马体体积,样本为216名个体,包括健康参与者(n = 171)和精神病患者(n = 45)。我们未观察到MIR137 PRS与这些与记忆功能相关的皮质厚度、表面积或海马体体积测量值之间存在显著关联;观察到PRS增加与全脑体积减小之间存在显著关联,且与诊断状态无关(R = 0.008,β = -0.09,p = 0.029)。但在多重检验校正后该结果不再显著。总之,我们的研究仅提供了提示性证据,表明与MIR137相互作用的风险变异会影响皮质结构。