Asthma Genetics: From Linear to Multifactorial Approaches

Annual Review of Medicine - Tập 59 Số 1 - Trang 327-341 - 2008
Stefano Guerra1, Fernando D. Martínez1
1Arizona Respiratory Center and Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona 85724;,

Tóm tắt

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.

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Annual Review of Medicine

Tập 59 Số 1

327-341

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