在犹他州涉及的超罕见误解变异 儿女多次受精神分裂症影响
Cathal Ormond1, Niamh M Ryan1, Elizabeth A Heron1
1Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Biological psychiatry global open science
|October 26, 2023
概括
家庭研究发现了与精神分裂症风险相关的特定基因变异. 对于平衡至关重要的ATP2B2基因在精神分裂症病例中显示出强烈的关联,这表明它在疾病发展中的作用.
科学领域:
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 精神分裂症外基因组测序元分析 (SCHEMA) 联盟在精神分裂症病例中发现了超罕见的变体.
- 基于家族的研究对于评估罕见变异是有价值的,因为在多重血统中具有共同的遗传影响.
研究的目的:
- 为了研究整个基因组测序数据,从受精神分裂症影响的家庭繁殖.
- 在血统中识别蛋白质编码变体和复制数变体,与精神分裂症共同分离.
主要方法:
- 在6个血统中对35个个体进行全基因组测序.
- 对于蛋白质编码变体的严格过管道和对副本数变体的基于家族的共识.
- 在SCHEMA数据集中对已识别的变异进行丰富分析.
主要成果:
- 在3个血统中,ATP2B2,SLC25A28和GSK3A的有害误解变异与疾病共分离.
- 在SCHEMA数据集中,ATP2B2在精神分裂症病例中显示出有害误解变异的显著丰富 (p=0.000072).
- ATP2B2与稳定有关,并在大脑组织中表达,预计不能容忍功能丧失变体.
结论:
- 在6种血统中,有3种基因可能会增加精神分裂症的风险,其中ATP2B2显示最强有力的证据.
- ATP2B2在平衡中的作用表明精神分裂症的潜在机制.
- 需要进一步的研究来探索其他导致精神分裂症的变异类.
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