Asthma genetics: From linear to multifactorial approaches

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)327-341
Number of pages15
JournalAnnual review of medicine
StatePublished - 2008


  • CD14
  • Complex disease
  • Interaction

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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