Leveraging gene-environment interactions and endotypes for asthma gene discovery.
Leveraging gene-environment interactions and endotypes for asthma gene discovery.
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DOI：
10.1016/j.jaci.2016.01.006
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Ober C
中科院分区：
文献类型：
--
作者：
Bønnelykke K;Ober C
Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs and the advantages of studying responses to asthma-associated exposures in clinical birth cohorts, as well as in cell models of GEIs, to dissect the context-specific nature of genotypic risks, to prioritize variants in genome-wide association studies, and to identify pathways involved in pathogenesis in subgroups of patients. We propose that such approaches, in spite of their many challenges, present great opportunities for better understanding of asthma pathogenesis and heterogeneity and, ultimately, for improving prevention and treatment of disease.
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DOI：
10.1183/09031936.00092410
发表时间：
2011-05
期刊：
The European respiratory journal
影响因子：
--
作者：
Bizzintino J;Lee WM;Laing IA;Vang F;Pappas T;Zhang G;Martin AC;Khoo SK;Cox DW;Geelhoed GC;McMinn PC;Goldblatt J;Gern JE;Le Souëf PN
通讯作者：
Le Souëf PN
DOI：
10.1016/j.jaci.2011.10.038
发表时间：
2012-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Bosco A;Ehteshami S;Panyala S;Martinez FD
通讯作者：
Martinez FD
影响因子：
14.2
作者：
Eder, W;Klimecki, W;Martinez, FD
通讯作者：
Martinez, FD
影响因子：
158.5
作者：
Bisgaard, Hans;Hermansen, Mette Northman;Pipper, Christian Bressen
通讯作者：
Pipper, Christian Bressen
影响因子：
158.5
作者：
Bouzigon, Emmanuelle;Corda, Eve;Demenais, Florence
通讯作者：
Demenais, Florence