Identification of rare variants of allergic rhinitis based on whole genome sequencing and gene expression profiling: A preliminary investigation in four families

Abstract

Background

Despite the success of genome-wide association studies for allergic rhinitis (AR), no definitive causal variants have been identified, and a substantial portion of the heritability of the disease is yet to be discovered.

Methods

Four families, each with at least 1 parent and one child suffering from dust mite (DM) AR, were recruited, and whole-genome sequencing was performed on samples from 9 eligible individuals from these families. Conjoint analysis was performed for existing gene expression profiling data in the literature and the whole genome sequencing data obtained for these individuals; for presence of family-specific variants segregating with AR and the pathways involved. Similar analyses were also performed with data obtained for 96 sporadic house dust mite (HDM) AR patients and 96 healthy controls.

Results

Three rare variants in three genes (FLT1_c.603A ​> ​T; VEGFB_c.322A ​> ​C; and ITGA2_c.502+1G ​> ​A), which are involved in Focal Adhesion pathway, were identified in affected, but not unaffected, subjects in two families. VEGFB_c.322A ​> ​C and/or ITGA2_c.502+1G ​> ​A were further detected in all DM AR patients but not in any healthy individuals in 1 family; which was further investigated for members. The 3 identified variants were not found in any of the sporadic DM AR patients or healthy controls.

Conclusion

Despite the relatively small sample size, this study has identified several potentially functional rare variants in AR candidate genes, and it provides a platform for future work in larger numbers of families and sporadic individuals for a better understanding of the genetic basis of AR.