Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
Curr Opin Allergy Clin Immunol. 2013 Oct;13(5):463-9. doi: 10.1097/ACI.0b013e328364ea5f.
A large number of genetic loci contribute towards an individual's susceptibility to asthma and other complex diseases. Genome-wide association studies (GWASs) have provided us with a wealth of loci associated with asthma susceptibility, asthma endotypes and responsiveness to asthma medications. The reproducibility of these genetic loci across different studies highlights the interplay of general and population-specific risk alleles in asthma. Although GWASs have been successful in identifying disease-associated loci, there is still large potential for such studies to provide further insights into asthma pathogenesis.
GWASs over the past year have extended study design well beyond the simple case-control and continuous phenotype association formats, for example, including interactions with environmental factors, integrating GWAS data with epigenetic data and GWASs in animal models, incorporating pathway analyses and utilising emerging sequencing technologies.
Moving beyond traditional GWAS formats is likely to significantly enhance our understanding of the genetic basis for asthma. This review discusses where we are after half a decade of asthma GWASs, and focuses on advances over the past year that show where the GWAS field is headed in the future.
综述目的：大量遗传基因座影响个体对哮喘和其他复杂疾病的易感性。全基因组关联研究（GWAS）为我们提供了丰富的与哮喘易感性、哮喘表型和对哮喘药物反应性相关的基因座。这些遗传基因座在不同研究中的可重复性突显了一般风险等位基因和特定人群风险等位基因在哮喘中的相互作用。虽然 GWAS 已成功确定了与疾病相关的基因座，但此类研究仍有很大潜力为哮喘发病机制提供更多的见解。
最新发现：过去一年的 GWAS 研究超越了简单的病例对照和连续表型关联设计，例如，包括与环境因素的相互作用、将 GWAS 数据与表观遗传数据和动物模型中的 GWAS 相结合、纳入途径分析以及利用新兴测序技术。
综述总结：超越传统的 GWAS 模式很可能会显著提高我们对哮喘遗传基础的理解。这篇综述讨论了在过去五年的哮喘 GWAS 之后我们所处的位置，并重点介绍了过去一年的进展，这些进展展示了 GWAS 领域未来的发展方向。
