Reviews and feature article
Genetics of asthma and allergy: What have we learned?

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The overall purpose of this review is to present an update on genetic approaches to understanding the susceptibility and expression (severity) of common diseases, such as asthma and allergy. Five key questions are addressed in this review: (1) What phenotypes are being studied? Multiple disease phenotypes in carefully characterized patients are required. (2) Are the same genes that are important in disease susceptibility important in disease severity? (3) Are there racial differences in disease expression and genetic susceptibility? (4) Are the genes important in normal variation in lung function important in asthma severity? (5) Are the genes important in other common diseases, such as chronic inflammatory diseases or chronic obstructive pulmonary disease, important in asthma or allergy? In addition, a discussion of some of current areas of research is presented, including the issue that current genome-wide association study results do not account for a significant portion of trait variability, the potential role of rare variants and large genome-sequencing studies, and pharmacogenetics: is there a role for basing treatment decisions on the results of genetic testing? Finally, the potential usefulness of DNA, personalized medicine, is discussed.

Section snippets

Key questions to be addressed

There are 5 key questions that will be addressed in this review (Table I), followed by a discussion of some of the newest areas of research in this field.

Key areas that are currently being studied

Several key areas of current research are important to address (Table II). An important issue is the concept of “missing variability,” which refers to what some investigators believe are disappointing results from GWASs. In many diseases the genes identified do not account for a large percentage of the observed trait variation.30 In other words, although statistically significant, the predictive value of using single genetic variants is very low. Possibly for some diseases, including asthma and

Summary

In Fig 3 an overall approach to genomic studies is presented.38 This is the current approach that is being used in our American Recovery and Reinvestment Act–funded Grand Opportunity NHLBI grant (principal investigators: Deborah Meyers, PhD; Eugene Bleecker, MD; Naftali Kaminski, MD; and Sally Wenzel, MD). There are additional important genomic approaches not discussed here, such as the use of gene expression profiles from relevant lung tissue to study susceptibility and severity, as well as

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    Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. SHearer, MD, PhD, and Donata Vercelli, MD

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    Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.