主要精神疾病,物质使用行为和长寿
Daniel B Rosoff1,2, Ali M Hamandi1, Andrew S Bell1
1Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
JAMA psychiatry
|June 18, 2024
概括
吸烟的遗传责任,但不是精神疾病,与长寿有关. 这项研究揭示了吸烟.
科学领域:
- 遗传学和衰老研究研究
- 精神病学流行病学 精神病学流行病学
- 分子生物学分子生物学
背景情况:
- 观察性研究表明,精神疾病和物质使用会影响长寿,这复杂化了对衰老的研究.
- 解开精神疾病,物质使用和寿命之间的遗传联系对于理解衰老过程至关重要.
研究的目的:
- 研究主要精神疾病,物质使用行为 (吸烟,饮酒) 和寿命之间的遗传关联.
- 探索这些关系的转录基因和蛋白质基因基础.
主要方法:
- 一个双样本的门德尔随机化 (MR) 研究,利用总结级的全基因组关联研究 (GWAS) 数据.
- 多基因组学分析包括来自欧洲祖先队伍的转录组和蛋白质组数据.
- 单变量和多变量MR模型评估抑郁症,双相情感障碍,精神分裂症,酒精使用和吸烟与长寿和表观遗传衰老加速 (EAA) 的遗传责任.
主要成果:
- 吸烟的遗传责任与长寿有显著的负面关联,与EAA增加有积极关联.
- 在主要精神疾病 (抑郁症,双相情感障碍,精神分裂症) 和寿命之间没有发现显著的遗传关联.
- 多基因组学分析确定了249个与吸烟相关的基因,包括新的点,以及染色质重塑和端粒维护中的涉及途径. 像LY6H和RIT2这样的优先级大脑蛋白与吸烟行为有关.
结论:
- 吸烟的遗传倾向,而不是精神疾病,与寿命的减少有关.
- 转录基因洞察力突出显示了调解吸烟对衰老影响的途径.
- 已确定的蛋白质组标可以指导新型戒烟疗法的开发.
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