Asthma risk has a clear hereditary component but, unexpectedly, the majority of reported associations between genetic variants and asthma have not been consistently replicated across studies. Methodological flaws have been indicated as a possible explanation for these inconsistencies. However, an alternative explanation is that the effects of genetic variants depend on other factors whose frequency and distribution vary, both across individuals and across populations. Within this framework, we review recent advances in asthma genetics and conclude that a paradigm shift is needed, because a static model in which the DNA sequence is associated with disease risk in a linear fashion fails to consider the interdependence of the diverse components of asthma risk. We propose an integrated approach, linking sequence variation to specific phenotypic manifestations of the disease by taking into account concurrent influences from biological systems and environmental factors that interact within specific developmental windows of opportunity.

中文翻译：

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哮喘遗传学：从线性方法到多因素方法。

哮喘风险具有明显的遗传成分，但出乎意料的是，报告的大多数遗传变异与哮喘之间的关联并未在所有研究中一致重复。方法上的缺陷已被指示为这些不一致的可能解释。然而，另一种解释是，遗传变异的影响取决于个体和群体之间频率和分布变化的其他因素。在此框架内，我们回顾了哮喘遗传学的最新进展，并得出结论，需要进行范式转换，因为静态模型（其中DNA序列与疾病风险呈线性关系）无法考虑哮喘风险的不同组成部分之间的相互依赖性。 。我们提出一种综合方法，