Editors' ChoiceAsthma Genetics

Thinking Globally About Asthma

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Science Translational Medicine  07 Sep 2011:
Vol. 3, Issue 99, pp. 99ec146
DOI: 10.1126/scitranslmed.3003140

We are all different, and clearly our human diversity is something to be celebrated. In clinical medicine, we have long known that many conditions are characterized by either increased prevalence or increased severity in different ancestral backgrounds. Despite strong epidemiological data, very little is currently known about the genetic and molecular mechanisms that underlie these ancestral disparities in human disease. This is an important issue because different molecular pathways will likely be more or less important in subjects of different ancestral backgrounds who have the same disease, and understanding these differences will allow us to personalize therapy. In a recent study, Torgerson et al. make progress on this front by studying the genetic basis of asthma across multiple North American populations and find both similarities and differences between ancestral backgrounds.

Asthma is a severe condition characterized by airway inflammation and episodic constriction of the airways, resulting in potentially life-threatening difficulty in breathing. Medical management is available, although not all patients respond completely, and there is no cure. Asthma is characterized by poorly understood differences in incidence across ancestral backgrounds, ranging from 7% in European Americans to 12% in African Americans. The authors performed a meta-analysis of existing genome-wide association data from European Americans, African Americans, and Latino Americans, including 5416 subjects with asthma. Five loci from this meta-analysis were strongly validated in a replication cohort of more than 12,000 subjects. Four of the asthma-associated loci corresponded to previously reported susceptibility loci: IL1RL1, IL33, TSLP, and 17q21. Thus, the authors confirm these as cross-population asthma risk factors. One previously unidentified association was detected in the PYHIN1 gene, and this association was specific to African ancestry populations. In fact, the associated PYHIN1 polymorphism was very rare on non-African chromosomes. PYHIN1 is an interferon-responsive gene involved in inflammatory pathways, and therefore a plausible candidate for asthma susceptibility.

Much of the genetic basis of asthma remains to be explained, although this study represents important progress in this area. The diversity between populations in genetic susceptibility should indicate molecular differences in pathogenesis, which will be important to consider as we begin translating new therapies to diverse populations with asthma.

D. G. Torgerson et al., Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat. Genet. 43, 887–892 (2011). [Abstract]

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