Pleitotropy和遗传推断的因果关系将多部位慢性疼痛与物质使用障碍联系起来
Dora Koller1,2,3, Eleni Friligkou4,5, Brendan Stiltner4,5
1Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. dora.koller@yale.edu.
Molecular psychiatry
|February 14, 2024
概括
慢性疼痛和物质使用障碍有共同的遗传联系,疼痛可能会增加酒精,大麻和烟草使用障碍的风险. 这项研究确定了有助于这些共享机制的特定遗传变异.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
背景情况:
- 慢性疼痛是一个重要的健康问题,经常与物质使用障碍 (SUD) 一起发生.
- 了解这种共同疾病的共同遗传基础对于开发有效的治疗方法和预防策略至关重要.
研究的目的:
- 研究多部位慢性疼痛 (MCP) 和各种SUD之间的遗传相关性和潜在因果关系.
- 确定特定的遗传位置和脑成像表型,与慢性疼痛和SUDs的并发症相关.
主要方法:
- 来自大型队列 (英国生物银行,MVP,PGC) 的全基因组关联统计数据用于MCP和SUD (AUD,CanUD,OUD,PTU).
- 进行了基于SNP的遗传性,遗传相关性 (rg) 和双向门德尔随机化 (MR) 分析.
- 使用成像数据进行全基因组类型和全脑关联分析,以确定共享的遗传变异.
主要成果:
- 在MCP和AUD,CanUD,OUD和PTU之间发现了显著的积极遗传相关性.
- MR分析表明双向关系,MCP对AUD,CanUD和PTU的影响更大.
- 在MCP和所有研究的SUD之间确定了两个类单核酸多态 (SNP),rs7652746 (IHO1) 和rs1248857 (CADM2).
- rs7652746也与小脑和杏仁体成像表型有关.
结论:
- 这项研究提供了第一个大规模的证据,证明了共享的遗传机制和慢性疼痛和物质使用障碍之间的潜在因果关系.
- 已识别的类变体和脑成像协会为这种并发症的生物学基础提供了新的见解.
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