自闭症谱系障碍和易怒肠综合征,多部位疼痛和疲劳之间的共同遗传结构和因果关系
Yiran Li1, Tian Xie2,3, Melissa Vos4
1Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. y.li@umcg.nl.
Translational psychiatry
|November 23, 2024
概括
自闭症谱系障碍 (ASD) 与功能性体力综合征 (FSS) (如IBS),疼痛和疲劳) 有共同的遗传联系. 虽然并未证明因果关系,但共同的遗传架构可能解释了它们频繁的共同发生.
科学领域:
- 精神病学是一个精神病学.
- 遗传学 是一个遗传学.
- 胃肠病学 胃肠病学
背景情况:
- 自闭症谱系障碍 (ASD) 经常与功能性体力综合征 (FSS) 一起发生,包括刺激性肠综合征 (IBS),多部位疼痛和疲劳.
- 遗传基础和ASD和FSS之间的因果关系仍未得到充分研究.
研究的目的:
- 通过大规模的全基因组关联研究 (GWAS) 数据,研究ASD和FSS之间的共享遗传架构和因果关系.
- 识别与ASD和FSS相关的新型遗传变异.
- 检查ASD多基因风险得分 (PRS) 与FSS表型的关联.
主要方法:
- 估计ASD和FSS之间的遗传相关性.
- 对GWAS (MTAG) 进行多特征分析,以确定新的遗传位置.
- 从GWAS和MTAG中导出ASD多基因风险得分 (PRS).
- 在生命线队列中,PRS与ASD和FSS表型的关联分析.
- 门德尔随机化 (MR) 分析以评估因果关系.
主要成果:
- 在ASD和IBS (rg=0.27),多部位疼痛 (rg=0.13) 和疲劳 (rg=0.33) 之间观察到显著的积极遗传相关性.
- MTAG确定了三个新的全基因组显著的自主位置,用于ASD (NEDD4L,MFHAS1,RP11-10A14.4).
- 来自GWAS和MTAG的ASD PRS与生命线队列中的ASD和FSS有关,而来自MTAG的PRS显示出更强烈的关联.
- 门德尔的随机化没有显示ASD和FSS之间的显著因果关系.
结论:
- 这项研究揭示了ASD和FSS之间显著的遗传关联,特别是IBS,多部位疼痛和疲劳.
- 一个共享的遗传架构可能有助于ASD和FSS之间观察到的并发症.
- 鉴于目前GWAS数据的局限性,需要进一步研究以增加统计能力,以阐明因果关系.
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