Evidence for a locus in 1p31 region specifically linked to the co-morbidity of asthma and allergic rhinitis in the EGEA study

Objective: A recent genome scan conducted in French EGEA families led to detect linkage of 1p31 to either asthma or allergic rhinitis (AR) and more significantly to asthma associated with AR. The goal of the present study was to assess formally whether 1p31 is a linkage region shared by two different diseases, asthma and AR, or whether it is specific to the co-morbidity asthma plus AR. Methods: We used two different statistical approaches: the Triangle Test Statistic (TTS) and the Predivided Sample Test (PST), to search for heterogeneity of linkage to 1p31 according to the affection status being defined by either the presence of the two diseases (asthma plus AR) or the presence of only one disease ('asthma only' or 'AR only' or 'asthma only or AR only'). Results: While no heterogeneity between the 'two diseases' phenotype and the 'one disease' phenotype was detected by the TTS, there was significant evidence for heterogeneity (p = 0.00007/0.002 after correction for multiple testing) using the PST. There was no indication of linkage in sib-pairs with 'one disease' only, while there was significant evidence for linkage in sib-pairs displaying asthma plus AR (p = 0.0002/0.0016 after correction). Conclusion: The present analysis shows that the co-morbidity, asthma plus AR, represents a phenotypic entity, distinct from asthma only or AR only, controlled by a genetic factor located on 1p31.