大脑结构和精神分裂症之间的遗传关系
Eva-Maria Stauffer1, Richard A I Bethlehem2,3, Lena Dorfschmidt2
1Department of Psychiatry, University of Cambridge, Cambridge, UK. ems206@cam.ac.uk.
Nature communications
|November 28, 2023
概括
研究人员确定了61个基因,将精神分裂症风险与大脑结构变异联系起来. 精神分裂症和大脑表型之间的遗传联系在关键的大脑网络枢纽中最强,这表明神经发育起源.
科学领域:
- 神经遗传学 神经遗传学
- 精神病学遗传学 精神病学遗传学
- 神经成像遗传学 神经成像遗传学
背景情况:
- 遗传因素会影响精神分裂症的风险,可能是通过对大脑结构的影响.
- 识别与精神分裂症和皮质现象型相关的特定基因对于理解这些联系至关重要.
研究的目的:
- 识别与精神分裂症和皮质结构指标相关的基因.
- 为了研究精神分裂症和大脑现象类型之间的遗传共变性.
- 探索精神分裂症遗传风险的神经发育基础.
主要方法:
- 利用全基因组关联研究 (GWAS) 对精神分裂症和磁共振成像 (MRI) 度量 (表面积,皮质厚度,神经元密度指数).
- 采用Hi-C合的MAGMA和全基因组部分最小平方分析来识别类基因和遗传共变.
- 进行了门德尔随机化分析,以评估因果关系,并比较不同疾病中的类关联.
主要成果:
- 确定了61个与精神分裂症和至少一个MRI指标显著相关的基因.
- 在大多数地区表明精神分裂症和皮质区域/厚度之间存在显著的遗传共变性.
- 发现基因协同变异在结构协同变异网络的枢纽中最强,相关基因被丰富为神经发育过程.
- 门德尔的随机化表明,在精神分裂症风险中,后带膜皮层区域变化的潜在因果作用.
- 对精神分裂症而言,与MRI指标的类药物相关性比对双相情感障碍,阿尔茨海默氏症或身高更为强烈.
结论:
- 特定的基因将精神分裂症与皮质结构的变异联系起来,特别是在关键的大脑网络中心.
- 神经发育过程与精神分裂症的遗传病因有关.
- 对特定皮质区域的遗传影响,如后带状皮质,可能因果关系地导致精神分裂症风险.
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