Genetic variation associated with the occurrence and progression of neurological disorders
Genetic variation associated with the occurrence and progression of neurological disorders
复制标题
DOI：
10.1016/j.neuro.2016.09.018
复制
发表时间：
2017-07-01
期刊：
影响因子：
3.4
通讯作者：
Krewski, Daniel
中科院分区：
文献类型：
--
作者：
Little, Julian;Barakat-Haddad, Caroline;Krewski, Daniel
本文概述了与14种神经系统疾病的发病和进展相关的遗传变异，主要集中在关联研究。这14种疾病在发病频率、发病年龄、病因和进展方面具有异质性。进展的证据远少于发作的证据。关于发病情况，其流行病学和家庭聚集模式各不相同。虽然肌营养不良症和亨廷顿氏病是单基因疾病，但对于其他12种疾病，只有一小部分病例与特定的遗传综合征或突变有关。除此之外，大多数病例仍有一定的家族聚集性。有相当大的差异，在数量的证据条件，并在条件内的基因。阿尔茨海默病、帕金森病、多发性硬化症和肌萎缩侧索硬化症的证据量最大。对于常见的复杂慢性疾病，全基因组关联研究发现，经验证的基因组区域占遗传率的比例很低。除了多发性硬化症（与其他免疫相关疾病共享几个易感基因座）、HLA-DRB 5变异与帕金森病和阿尔茨海默病相关以及C9 orf 72重复扩增与ALS和额颞叶变性相关之外，几乎没有证据表明基因座与一种以上的神经系统疾病或其他疾病一致相关。除了脊柱裂，母亲MTHFR基因型与后代的风险相关，并证实了叶酸在病因学中的重要性的其他证据，很少有证据表明遗传变异影响的途径与已知的生活方式或环境暴露有关。(C)2016由Elsevier B. V.出版
This paper presents an overview of genetic variation associated with the onset and progression of 14 neurological disorders, focusing primarily on association studies. The 14 disorders are heterogeneous in terms of their frequency, age of onset, etiology and progression. There is substantially less evidence on progression than onset. With regard to onset, the conditions are diverse in terms of their epidemiology and patterns of familial aggregation. While the muscular dystrophies and Huntington's disease are monogenic diseases, for the other 12 conditions only a small proportion of cases is associated with specific genetic syndromes or mutations. Excluding these, some familial aggregation remains for the majority of cases. There is considerable variation in the volume of evidence by condition, and by gene within condition. The volume of evidence is greatest for Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. As for common complex chronic diseases, genome wide association studies have found that validated genomic regions account for a low proportion of heritability. Apart from multiple sclerosis, which shares several susceptibility loci with other immune-related disorders, variation at HLA-DRB5 being associated both with Parkinson's disease and Alzheimer's disease, and the association of the C9orf72 repeat expansion with ALS and frontotemporal degeneration, there was little evidence of gene loci being consistently associated with more than one neurological condition or with other conditions. With the exception of spina bifida, for which maternal MTHFR genotype is associated with risk in the offspring, and corroborates other evidence of the importance of folate in etiology, there was little evidence that the pathways influenced by genetic variation are related to known lifestyle or environmental exposures. (C) 2016 Published by Elsevier B.V.