用皮质大脑形态剖析常见的共同遗传结构
Naz Karadag1, Espen Hagen1, Alexey A Shadrin1
1From the Institute of Clinical Medicine (N.K., E.H., A.A.S., D.M., K.S.O.C., Z.R., G.K., N.P., S.B., V.F., N.E.S., O.F., O.A.A., O.B.S.), NORMENT, University of Oslo; K.G. Jebsen Centre for Neurodevelopmental Disorders (A.A.S., O.A.A.), University of Oslo and Oslo University Hospital, Norway; Faculty of Health (D.M.), School of Mental Health and Neuroscience, Maastricht University, Netherlands; Department of Neurology (K.H., E.T.), Oslo University Hospital; Faculty of Medicine (E.T.), University of Oslo; Division of Mental Health and Addiction (N.E.S., O.A.A., O.B.S.), Oslo University Hospital; Department of Psychiatric Research (N.E.S.), Diakonhjemmet Hospital; Department of Medical Genetics (S.D.), Oslo University Hospital, Norway; Department of Clinical Science (S.D.), NORMENT, University of Bergen, Norway; Department of Cognitive Science (A.M.D.); Multimodal Imaging Laboratory (A.M.D.); Department of Psychiatry (A.M.D.); Department of Neurosciences (A.M.D.), University of California, San Diego; and Department of Informatics (O.F.), Center for Bioinformatics, University of Oslo, Norway.
一般性和大脑皮层厚度 (TH) 和表面积 (SA) 之间存在遗传重叠. 共同的遗传因素可能是患者观察到的皮质异常的基础.
科学领域:
- 神经遗传学 神经遗传学
- 发病学 (Epileptology) 是一个专业的学科.
- 量化遗传学 量化遗传学
背景情况:
- 与皮质厚度 (TH) 和表面积 (SA) 的变化有关.
- 连接和皮质形态的潜在生物机制仍然不清楚.
- 研究共同的遗传影响对于理解这些关系至关重要.
研究的目的:
- 确定常见和皮质形态 (TH和SA) 之间的共同遗传影响的程度.
- 为了确定和皮层特征之间重叠的特定遗传位置.
- 探索这些复杂的表型背后的遗传结构.
主要方法:
- 分析了大量 (n=69,995) 和皮质形态 (n=32,877) 的全基因组关联研究 (GWAS) 数据.
- 使用高斯混合模型 (MiXeR) 和结合错误发现率 (conjFDR) 来评估遗传重叠并确定共享的位置.
- 对已识别的位点进行了生物检查,并对独立样本进行了验证.
主要成果:
- 患者表现出比SA和TH更多基因的结构.
- 在SA和遗传通用性 (GGE),所有和青少年肌细胞性 (JME) 之间检测到大量的遗传重叠.
- 在TH和GGE之间也发现了显著的重叠,所有,和JME,确定了许多共享的位置,包括和皮质形态学的新位置.
结论:
- 一般性和皮层形态之间存在广泛的遗传重叠.
- 这些发现表明,共同的遗传因素有助于的皮质异常.
- 复杂的遗传关系意味着共同影响的作用方向混合.
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