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哮喘表型和治疗反应的基因组预测指标

Genomic Predictors of Asthma Phenotypes and Treatment Response.

作者信息

Hernandez-Pacheco Natalia, Pino-Yanes Maria, Flores Carlos

机构信息

Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.

Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.

出版信息

Front Pediatr. 2019 Feb 5;7:6. doi: 10.3389/fped.2019.00006. eCollection 2019.

Abstract

Asthma is a complex respiratory disease considered as the most common chronic condition in children. A large genetic contribution to asthma susceptibility is predicted by the clustering of asthma and allergy symptoms among relatives and the large disease heritability estimated from twin studies, ranging from 55 to 90%. Genetic basis of asthma has been extensively investigated in the past 40 years using linkage analysis and candidate-gene association studies. However, the development of dense arrays for polymorphism genotyping has enabled the transition toward genome-wide association studies (GWAS), which have led the discovery of several unanticipated asthma genes in the last 11 years. Despite this, currently known risk variants identified using many thousand samples from distinct ethnicities only explain a small proportion of asthma heritability. This review examines the main findings of the last 2 years in genomic studies of asthma using GWAS and admixture mapping studies, as well as the direction of studies fostering integrative perspectives involving omics data. Additionally, we discuss the need for assessing the whole spectrum of genetic variation in association studies of asthma susceptibility, severity, and treatment response in order to further improve our knowledge of asthma genes and predictive biomarkers. Leveraging the individual's genetic information will allow a better understanding of asthma pathogenesis and will facilitate the transition toward a more precise diagnosis and treatment.

摘要

哮喘是一种复杂的呼吸系统疾病,被认为是儿童中最常见的慢性病。亲属中哮喘和过敏症状的聚集以及双胞胎研究估计的高达55%至90%的高疾病遗传率预示着遗传因素对哮喘易感性有很大影响。在过去40年里,人们利用连锁分析和候选基因关联研究对哮喘的遗传基础进行了广泛研究。然而,多态性基因分型密集阵列的发展使得向全基因组关联研究(GWAS)的转变成为可能,在过去11年里,GWAS已经发现了几个意想不到的哮喘基因。尽管如此,利用来自不同种族的数千个样本确定的目前已知的风险变异仅解释了哮喘遗传率的一小部分。本综述探讨了过去两年在哮喘基因组研究中使用GWAS和混合映射研究的主要发现,以及促进涉及组学数据的综合观点的研究方向。此外,我们讨论了在哮喘易感性、严重程度和治疗反应的关联研究中评估整个遗传变异谱的必要性,以便进一步提高我们对哮喘基因和预测性生物标志物的认识。利用个体的遗传信息将有助于更好地理解哮喘发病机制,并将促进向更精确的诊断和治疗的转变。

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