与正常压力水脑相关的风险变异:在FinnGen队列中进行全基因组协会研究
Joel Räsänen1, Sami Heikkinen1, Kiira Mäklin1
1From the Department of Neurosurgery (J. Räsänen, K.M., V.E.K., M.O., J.E.J., V.L.), Kuopio University Hospital and Institute of Clinical Medicine-Neurosurgery, and Institute of Biomedicine (S. Heikkinen, K.M., A.L., T.K., M.H.), University of Eastern Finland, Kuopio; Institute for Molecular Medicine Finland (FIMM) (J.M., A.P.), Helsinki Institute of Life Science (HiLIFE), University of Helsinki; Department of Neurology (A.J.), Clinical Neurosciences, Helsinki University Hospital and University of Helsinki, Finland; Univ. Lille (B.G.-B., C.B., J.-C.L.), Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, France; Department of Neurosurgery (M.O., K.L., J.S.), University of Helsinki and Helsinki University Hospital; Clinical Neurosciences (C.A., J.F., A.K., J. Rinne), Department of Neurosurgery, University of Turku and Turku University Hospital; Department of Neurosurgery (A.R.), Tampere University Hospital; Unit of Clinical Neuroscience (M.K., M.v.u.z.F.), Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital; Finnish Institute for Health and Welfare (THL) (M.P.); University of Helsinki (M.P.); Department of Neurosciences (A.M.K., A.M.P.), University of Helsinki; Department of Geriatrics (A.M.K.), Helsinki University Hospital; NeuroCenter (A.M.K.), Kuopio University Hospital; Institute of Clinical Medicine-Neurology (V.J., H.S.), University of Eastern Finland; School of Medicine (A.M.), Institute of Clinical Medicine, Pathology and Forensic Medicine, and Translational Cancer Research Area, University of Eastern Finland; Department of Clinical Pathology (A.M.), Kuopio University Hospital; Unit of Clinical Medicine (S. Helisalmi), University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery (P.K.E.), Oslo University Hospital-Rikshospitalet; Institute of Clinical Medicine (P.K.E.), Faculty of Medicine, and KG Jebsen Centre for Brain Fluid Research (P.K.E.), University of Oslo, Norway; Analytical and Translational Genetics Unit (A.P., M.I.K.), Department of Medicine, Massachusetts General Hospital, Boston; Program in Medical and Population Genetics (A.P., M.I.K.), and Stanley Center for Psychiatric Research (A.P., M.I.K.), Broad Institute for Harvard and MIT, Cambridge, MA.
这项全基因组关联研究确定了六个与正常压力头症 (NPH) 相关的基因区域. 慢性头症最大GWAS的这些发现为NPH病因提供了新的见解.
科学领域:
- 遗传学 是一个遗传学.
- 神经学 神经学
- 流行病学 流行病学
背景情况:
- 针对慢性水头的大型全基因组关联研究 (GWAS) 是有限的.
- 正常压力脑症 (NPH) 是一种影响步态,认知和泌尿功能的神经疾病.
研究的目的:
- 进行第一个大规模的全基因组关联研究 (GWAS) 针对正常压力脑病 (NPH).
- 确定与NPH和异常性NPH (iNPH) 相关的遗传位置.
主要方法:
- 利用一个病例控制设计与FinnGen数据 (473,691个人) 和英国生物库数据进行复制.
- 使用ICD-10代码G91.2确定了NPH病例,并对异常性NPH (iNPH) 进行了敏感性分析.
主要成果:
- 鉴定了与NPH相关的6个显著基因区域 (p < 5.0e-8),在分析中复制.
- 顶部位置包括SLCO1A2,AMZ1/GNA12,MLLT10,CDCA2,C16orf95和PLEKHG1.1附近的基因.
- 在iNPH灵敏度分析中,四个位点仍然是显著的,具有相似的效果大小和等位基频率.
结论:
- 该研究确定了6个与NPH显著相关的位置,代表了迄今为止慢性水头中最大的GWAS.
- 这些位置附近的基因与血脑屏障和血脑脊髓液屏障功能有关.
- 确定的位点可能是iNPH的风险决定因素,尽管它们的确切作用需要进一步调查.
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