刺激性肠综合征和精神疾病之间的共同遗传结构揭示了肠-大脑轴的分子路径
Markos Tesfaye1,2, Piotr Jaholkowski3, Guy F L Hindley3,4
1NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. m.t.woldeyohannes@medisin.uio.no.
Genome medicine
|August 1, 2023
概括
这项研究揭示了刺激性肠综合征 (IBS) 和精神疾病之间广泛的遗传重叠,确定了新的遗传风险位置. 这些发现增强了对IBS病理生理学的理解,并可能导致个性化治疗.
科学领域:
- 遗传学 遗传学 是一个
- 胃肠病学 胃肠病学
- 精神病学是一个精神病学.
背景情况:
- 刺激性肠综合征 (IBS) 经常与精神病和胃肠道疾病同时发生.
- 虽然全基因组关联研究 (GWAS) 已经确定了一些IBS遗传风险变体,但大多数遗传性仍然无法解释.
- 之前的研究还没有完全量化IBS和其他疾病之间除了广泛的遗传相关性之外的遗传重叠.
研究的目的:
- 描述IBS的遗传结构.
- 调查IBS和精神病/胃肠道表型之间的遗传重叠.
- 通过利用共享的遗传因素来确定IBS的新型基因组风险位置.
主要方法:
- 使用了GWAS对IBS (53,400例,433,201例对照) 和相关表型的总结统计.
- 采用双变因混合模型来分析遗传架构和重叠.
- 应用条件/结合式错误发现率 (condFDR/conjFDR) 和FUMA用于位置发现和功能分析.
主要成果:
- 肠胃综合症具有高度多基因性,通过对精神病和胃肠道疾病的条件确定了132个独立的相关位点.
- 在IBS和精神疾病之间发现了广泛的多基因重叠,在胃肠道疾病中也发现了较小的重叠.
- 确定了70个IBS和精神疾病之间共享的独特位置,为神经和免疫系统通路进行了丰富.
结论:
- 在IBS和精神病/胃肠道表型之间存在广泛的多基因重叠,超过了以前的遗传相关性估计.
- 利用这种重叠导致发现了新的IBS遗传位点,涉及超越肠-大脑轴的途径.
- 研究结果表明,遗传差异可能是IBS亚型的基础,并为个性化干预铺平了道路.
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