TY - JOUR
T1 - Asthma genetics
T2 - From linear to multifactorial approaches
AU - Guerra, Stefano
AU - Martinez, Fernando D.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - CD14
KW - Complex disease
KW - Interaction
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U2 - 10.1146/annurev.med.59.060406.213232
DO - 10.1146/annurev.med.59.060406.213232
M3 - Review article
C2 - 17845134
AN - SCOPUS:39649123754
SN - 0066-4219
VL - 59
SP - 327
EP - 341
JO - Annual review of medicine
JF - Annual review of medicine
ER -