神经精神病和与胰岛素抵抗有关的疾病之间遗传共享的局部模式
Giuseppe Fanelli1,2,3, Barbara Franke1,2,4, Chiara Fabbri3
1Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
胰岛素抵抗 (IR) 和神经精神疾病具有共同的遗传联系,在109个基因组区域中确定. 这些区域涉及免疫,代谢和信号通路,提供新的治疗点.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 与胰岛素抵抗 (IR) 相关的代谢状况和神经精神疾病的同时发生构成了公共卫生挑战.
- 新出现的证据表明遗传联系,但涉及的基因组区域和生物功能在很大程度上仍然未知.
研究的目的:
- 确定基因组区域和生物功能,这些基因区域和生物功能是IR相关疾病和神经精神疾病之间的遗传联系的基础.
- 探索潜在的共同因果变体和治疗点.
主要方法:
- 在对代谢和神经精神疾病的大规模全基因组关联研究 (GWASs) 数据上利用[共]变异关联局部分析 (LAVA).
- 进行了基因映射,功能性基因组分析和对重要位置的同地化分析.
主要成果:
- 确定了109个独特的基因组区域,在IR相关疾病和神经精神疾病之间存在显著的局部遗传相关性.
- 在免疫-炎症,胰岛素信号和脂质代谢途径中发现了丰富.
- 优先考虑了10个区域,其中有SLC39A8和HLA-DRB1.1等可药物基因附近的潜在共同因果变异.
结论:
- 这项研究突出了IR-神经精神病学多病症的复杂遗传结构.
- 倡导一种综合性疾病模型,并建议针对共同遗传途径的新型研究和治疗策略.
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