与双相情感障碍治疗反应相关的遗传变异:全基因组关联研究
Liping Hou1, Urs Heilbronner2, Franziska Degenhardt3
1Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Lancet (London, England)
|January 26, 2016
概括
在21号染色体上发现了双极性障碍中反应的遗传标志物. 这些发现可能会导致个性化治疗的生物标志物,改善双相情感障碍的临床治疗.
科学领域:
- 遗传学
- 精神病学
- 药物基因组学
背景情况:
- 是双相情感障碍的主要治疗方法,
- 人们怀疑遗传因素会影响治疗的疗效.
- 之前试图识别可靠的反应基因标记是没有成功的.
研究的目的:
- 进行全基因组关联研究 (GWAS),以确定双极性疾病中与反应相关的遗传标记.
- 在一个独立的队列中验证潜在的遗传发现.
主要方法:
- 一个大规模的GWAS涉及2563个双相情感障碍患者来自国际遗传学联盟 (ConLiGen).
- 使用全基因组基因类型和归算来分析常见的单核酸多态 (SNP).
- 关联测试与分类和连续响应测量 (Alda尺度).
- 跨研究批次的结果的元分析和前性队列的验证.
主要成果:
- 在21号染色体上含有四个链接的SNP的显著位点与反应有关 (例如rs79663003,p=1.37×10−8).
- 在前性研究中,携带响应相关基因的患者复发率明显较低 (p=0. 03268,HR=3. 8).
结论:
- 确定的遗传区域包括两个长非编码RNA (lncRNA) 基因,AL157359.3和AL157359.4.
- LncRNA正在成为中枢神经系统 (CNS) 中基因表达的关键调节者.
- 这些发现代表了开发针对双相情感障碍的个性化治疗生物标志物的潜在步骤,需要对其生物机制和临床实用性进行进一步的研究.
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