A single-nucleotide polymorphism influences brain morphology in drug-naive patients with major depressive disorder
A single-nucleotide polymorphism influences brain morphology in drug-naive patients with major depressive disorder
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DOI：
10.2147/ndt.s204461
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发表时间：
2019-01-01
影响因子：
3.2
通讯作者：
Yoshimura, Reiji
中科院分区：
文献类型：
--
作者：
Katsuki, Asuka;Kakeda, Shingo;Yoshimura, Reiji
目的：最近，一项全基因组关联研究成功地发现了与抑郁症（MDD）相关的遗传变异。该研究确定了17个独立的单核苷酸多态性（SNP）与MDD的诊断显著相关。这些SNP被预测为富集在中枢神经系统中表达的基因中，并且在与神经发育相关的转录调节中起作用。本研究采用磁共振成像（MRI）技术，对47例MDD患者和42例健康对照者（HC）的17个SNPs与脑形态计量学的相关性进行了研究。所有参与者均接受T1加权结构MRI和基因分型。与区域皮质厚度相关的基因型诊断的相互作用进行了评估，使用基于体素的形态学为17 SNPs.Results：关于rs301806，在RERE基因组区域的SNP，我们发现一个显着差异的基因型效应在右侧眶额和中央后叶之间的诊断组。在测试了所有可能的诊断比较后，这些区域的基因型-诊断相互作用显示，MDD组相对于HC组的皮质厚度减少在T/T个体中显著大于C携带者。对于其他SNP，没有大脑区域的基因型效应显着不同的两个groups.Conclusions：我们发现，一个RERE基因SNP与皮质厚度的减少在右侧眶额和中央后叶的药物初治MDD患者。RERE基因多态性和基因-环境交互作用可能对MDD患者的脑结构产生影响。
Objective: Recently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-naive patients with MDD and healthy controls (HCs).Methods: Forty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype-diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs.Results: Regarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype-diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups.Conclusions: We found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-naive patients with MDD. The effects of RERE gene polymorphism and gene-environment interactions may exist in brain structures of patients with MDD.