Genotype *Sex* Environment: unraveling the complexity of genetic associations with asthma

Published Online: July 28, 2011

Sex differences in the incidence, prevalence, and severity of asthma are well established, but knowledge of the underlying molecular and genetic basis of these differences remains limited.

In an upcoming issue of The Journal of Allergy and Clinical Immunology (JACI), Loisel et al investigate the genetic architecture of sex differences in asthma risk using genetic variation in the asthma candidate gene, interferon-gamma (IFNG). They show that sex and IFNG genotype interact to influence childhood asthma risk in a high-risk birth cohort of children, and then replicate this finding in an independent sample of subjects with childhood onset asthma.

Interestingly, the observed genotype-by-sex interaction was itself influenced by early-life environmental exposures, specifically the occurrence of viral wheezing illnesses, suggesting that genotype-by-sex interactions can be environment-specific.

Finally, the authors document similar genotype-by-sex interaction effects on IFN-g protein expression in vitro, providing insight into the mechanistic basis of this interaction. These results highlight the importance of considering genotype interactions with sex and environmental factors in genetic studies of complex diseases such as asthma.


The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

AAAAI - American Academy of Allergy Asthma & Immunology