Dept of Psychiatry & Neuropsychiatric Genetics Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
Neurosci Lett. 2013 Jan 4;532:33-8. doi: 10.1016/j.neulet.2012.08.065. Epub 2012 Sep 13.
The Schizophrenia Psychiatric Genome-wide Association (GWAS) Consortium recently reported on five novel schizophrenia susceptibility loci. The most significant finding mapped to a micro-RNA, MIR-137, which may be involved in regulating the function of other schizophrenia and bipolar disorder susceptibility genes.
We genotyped 821 patients with confirmed DSM-IV diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective disorder for the risk SNP (rs1625579) and investigated the clinical profiles of risk allele carriers using a within-case design. We also assessed neurocognitive performance in a subset of cases (n=399) and controls (n=171).
Carriers of the risk allele had lower scores for an OPCRIT-derived positive symptom factor (p=0.04) and lower scores on a lifetime measure of psychosis incongruity (p=0.017). Risk allele carriers also had more cognitive deficits involving episodic memory and attentional control.
This is the first evidence that the MIR-137 risk variant may be associated with a specific subgroup of psychosis patients. Although the effect of this single SNP was not clinically relevant, investigation of the impact of carrying multiple risk SNPs in the MIR-137 regulatory network on diagnosis and illness profile may be warranted.
精神分裂症精神病基因组关联 (GWAS) 联盟最近报告了五个新的精神分裂症易感性位点。最显著的发现映射到 micro-RNA,MIR-137,它可能参与调节其他精神分裂症和双相情感障碍易感性基因的功能。
我们对 821 名经 DSM-IV 确诊的精神分裂症、单相双相情感障碍 I 和分裂情感障碍患者进行了风险 SNP(rs1625579)的基因分型,并使用病例内设计研究了风险等位基因携带者的临床特征。我们还在一部分病例 (n=399)和对照 (n=171)中评估了神经认知表现。
风险等位基因携带者的 OPCRIT 衍生阳性症状因子评分较低 (p=0.04),一生中精神错乱程度的评分也较低 (p=0.017)。风险等位基因携带者的认知缺陷也更多,涉及到情景记忆和注意力控制。
这是第一个证据表明 MIR-137 风险变体可能与特定亚组的精神病患者有关。尽管这个单一 SNP 的影响在临床上并不显著,但研究 MIR-137 调节网络中携带多个风险 SNP 对诊断和疾病特征的影响可能是必要的。