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伴随性疾病改变了焦虑症和严重抑郁症之间的遗传关系
Markos Tesfaye1,2, Alexey Shadrin1,3, Nadine Parker1
1Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
medRxiv : the preprint server for health sciences
|November 28, 2024
概括
在对焦虑症 (ANX) 和严重抑郁症 (MD) 的遗传研究中排除并发症,揭示了不同的遗传关系. 焦虑障碍可能会因果影响严重抑郁症,建议针对性干预.
科学领域:
- 精神病学遗传学 精神病学遗传学
- 基因组流行病学 基因组流行病学
- 临床神经科学 临床神经科学
背景情况:
- 焦虑症 (ANX) 和严重抑郁症 (MD) 经常同时发生,使遗传关联研究复杂化.
- 在基因分析中排除并发病例可能会澄清疾病特定的生物途径和因果关系.
研究的目的:
- 调查焦虑症和严重抑郁症之间的独特遗传关系和因果关系,比较分析与并发症病例和没有并发症病例.
- 评估共发病如何影响ANX和MD的遗传架构和多基因风险评分 (PRS).
主要方法:
- 全基因组关联研究 (GWAS) 针对来自英国生物银行的焦虑症和严重抑郁症队列进行.
- 在挪威的母亲,父亲和儿童队列 (MoBa) 中生成和测试了疾病特异性多基因风险评分 (PRS).
- 基因相关性 (LDSC) 和门德尔随机化分析被用来推断因果关系.
主要成果:
- 只有焦虑障碍和只有严重抑郁症之间的遗传相关性比共患病例 (0.90) 的遗传相关性低 (0.53).
- 只有焦虑障碍对只有严重抑郁症有因果作用,但反之并非如此;并发症病例显示双向因果关系.
- 来自疾病特异性队列的PRS显示与诊断和症状的差异关联,与共发病队列的PRS不同.
结论:
- 焦虑症和严重抑郁症的遗传基础在排除并发病例时更加明显.
- 焦虑障碍可能在严重抑郁症中起因作用,这种关系被伴随性疾病所掩盖.
- 特定疾病的基因分析对于发现精确的生物机制和指导针对精神疾病的有针对性的临床干预至关重要.
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