Abstract
Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.
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Acknowledgements
Detailed acknowledgements and funding details for each contributing study are provided in the Supplementary Note.
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Study design and management: K.B., J.W., M.S., and D.P.S. Meta-analyses: M.S. and J.W. Manuscript writing: K.B., J.W., M.S., J.A.C., J.T., L.E.J., and M.A.F. Systems biology analyses: J.W., J.A.C., J.T., L.E.J., J.M.M., S.B.-G., and D.T. Data collection, analysis, and design in the individual contributing studies: K.B., J.W., M.S., J.A.C., C.F., A. Abdellaoui, T.S.A., A.C.A., A.F.S.A., J.M.A., A. Arnold, A.B.-L., H. Baurecht, C.E.M.v.B., E.R.B., D.I.B., S. Bunyavanich, E.B., Z.C., I.C., A.C., H.T.d.D., S.C.D., J.D., L.D., M.J.E., W.J.G., C.G., F.G., R.G., H.G., T.H., J. Heinrich, J. Henderson, N.H.-P., D.A.H., P.H., M.I., V.W.V.J., M.-R.J., D.L.J., I.J., M.K., J.K., A.K., Y.-A.L., A.M.L., X.L., F.L.-D., E.M., D.A.M., R.M., D.L.N., E.A.N., T.P., L.P., C.E.P., G.P., M.P.-Y., N.M.P.-H., F.R., A.S., K.S., J.S., G.S., E.T., P.J.T., C.T., M.T., J.Y.T., C.A.W., S. Weidinger, S. Weiss, G.W., L.K.W., C.O., M.A.F., H. Bisgaard, D.P.S., The 23andMe Research Team and AAGC collaborators. Immunological interpretation: N.S. and S. Brix. Gene-expression analysis: M.G. and J.D. Protein modeling: K.K.J.
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G.S., I.J., and K.S. are affiliated with deCODE genetics/Amgen and declare competing financial interests as employees. C.T., D.A.H., J.Y.T., and the 23andMe Research Team are employees of and hold stock and/or stock options in 23andMe, Inc. L.P. has received a fee for participating in a scientific-input engagement meeting from Merck Sharp & Dohme Limited, outside of this work.
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Waage, J., Standl, M., Curtin, J.A. et al. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nat Genet 50, 1072–1080 (2018). https://doi.org/10.1038/s41588-018-0157-1
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DOI: https://doi.org/10.1038/s41588-018-0157-1
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