精神分裂症和白细胞计数之间的共同遗传位置表明遗传决定的系统性免疫异常
Nils Eiel Steen1,2, Zillur Rahman1,2, Attila Szabo1,3
1NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Schizophrenia bulletin
|June 15, 2023
概括
影响白细胞 (WBC) 数量的遗传因素与精神分裂症 (SCZ) 风险有关. 这表明免疫系统参与SCZ,可能使针对患者亚组的向治疗成为可能.
科学领域:
- 精神病学是一个精神病学.
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- 精神分裂症 (SCZ) 越来越多地与免疫系统机制有关.
- 全基因组关联研究 (GWAS) 已经确定了SCZ和免疫表型之间的共同遗传变异.
- 研究共享的遗传架构可以阐明免疫系统在SCZ病变发生中的作用.
研究的目的:
- 使用先进的统计方法,识别SCZ和白细胞 (WBC) 计数之间的共享遗传变异.
- 了解SCZ和免疫细胞亚型之间的遗传重叠和潜在因果关系.
- 探索SCZ和免疫调节中共享的遗传因素的功能影响.
主要方法:
- 使用GWAS数据用于SCZ和WBC计数.
- 应用了链接不平衡得分回归,有条件的错误发现率和双变因果混合模型.
- 进行了双样本的门德尔随机化,以评估因果关系.
主要成果:
- 在SCZ和WBC计数之间确定了383个共享的基因位置,其中53%显示一致的效果方向.
- 在所有WBC亚型中发现了显著的遗传重叠,包括淋巴细胞,中性细胞,单细胞,乙酸细胞和基酸细胞.
- 功能分析指出细胞功能和翻译调节是共享的机制.
结论:
- 影响白细胞计数的遗传因素与SCZ风险有关,突出显示了免疫机制在SCZ中的作用.
- 这些发现表明,基于针对性治疗的免疫特征,可能存在患者分层的可能性.
- 这项研究为开发针对特定SCZ亚组的新型免疫向治疗提供了基础.
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