Highly significant linkage to chromosome 3q13.31 for rhinitis and related allergic diseases

Background: Allergic diseases such as asthma and rhinitis have closely related phenotypes and often occur with atopy. They show strong familial and intra-individual clustering, suggesting overlapping disease aetiology. Various loci and candidate genes have been suggested to underlie allergy. Many or all are still inconclusive. Following genome-wide scans on multiple phenotypes, we previously suggested that chromosome 3q13.12-q21.2 harbours an allergy locus. Objective: To identify candidate loci in the Danish population, two additional independent sets of sib-pair families were fine-scale mapped in candidate regions showing maximum likelihood scores (MLS)>= 1.5 in the genome-wide scans. Results: Twenty eight microsatellite markers in a denser map on chromosome 3q were analysed in 236 allergy sib-pair families including 125 sib pairs with rhinitis. We report significant evidence for linkage to chromosome 3q13.31 for rhinitis (MLS 5.55, identity by descent (IBD) 63.9%) and atopy (increased specific immunoglobulin E) (MLS 3.71, IBD 61.7%). We obtained an MLS of 5.1 (IBD 67.3%) at 3q13.31 when sib pairs with both rhinitis and atopy were analysed. Conclusion: This study reports the first statistically significant evidence for a genetic susceptibility locus for rhinitis and to our knowledge shows the most significant evidence to date of linkage for any allergy phenotype.