Abstract
Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.
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A full list of acknowledgments for each study is given in the Supplementary Note.
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Study-level data analysis: K.B., T.H.P. (meta-analysis and systems biology analyses), R. Granell (meta-analysis), D.P.S., A.C.A. (systems biology analyses), A.L., J.A.C., N.M.W., M.S., M. Kerkhof, B.K.B., M. Kaakinen, P. Sleimann, G.T., K. Schramm, E.K.-M., A.S., L.C., C.S.T., B.P.F., R. Gupta, M.B., S.W., H.H., D.S.P., A.C., G.H.K. and N.T. Study design: K.B., M.C.M., T.H.P., D.P.S., A.L., B.K.B., E.K.-M., A.S., C.F.R., G.W.M., S.C.D., P.E., M.J.A., J.C.K., R. Gupta, P.J.T., J.N.H., M.B., S.W., H.H., J. Heinrich, D.S.P., A.C., C.E.P., M.-R.J., G.H.K., N.T., M.A.F., H.B. and A.J.H. Writing manuscript: K.B., T.H.P., R. Granell, D.P.S., A.C.A., A.L., J.A.C., G.H.K., N.T., M.A.F., H.B. and A.J.H. Data collection: K.B., M.C.M., D.P.S., A.L., I.J., B.K.B., U.T., A.S., J. Hui, E.H.W., D.L.D., G.J., L.P., C.F.R., J.P., E.T., A.-L.H., S.C.D., L.L.H., C.H., A.J., B.P.F., J.C.K., M.J.A., P.J.T., P.H., P. Sly, M.B., H.H., K. Stefansson, J. Heinrich, D.S.P., A.C., M.-R.J., G.H.K., H.B. and A.J.H. Genotyping: K.B., A.L., J.A.C., I.J., P. Sleimann, U.T., S.B., E.K.-M., A.S., B.S.P., C.M.T.T., S.M.R., W.L.M., G.W.M., L.L.H., J.P.K., M.W., H.H., K. Stefansson, A.C., C.E.P., M.-R.J., G.H.K. and H.B. Revising and reviewing manuscript: K.B., M.C.M., T.H.P., R. Granell, D.P.S., A.C.A., A.L., J.A.C., N.M.W., M.S., M. Kerkhof, I.J., B.K.B., M. Kaakinen, P. Sleimann, G.T., U.T., K. Schramm, S.B., E.K.-M., A.S., B.S.P., L.C., J. Hui, E.H.W., C.M.T.T., D.L.D., G.J., S.M.R., W.L.M., L.P., C.F.R., J.P., C.S.T., E.T., G.W.M., A.-L.H., S.C.D., L.L.H., C.H., J.P.K., P.E., A.J., M.W., M.J.A., B.P.F., J.C.K., R. Gupta, P.J.T., P.H., P. Sly, J.N.H., M.B., S.W., H.H., K. Stefansson, J. Heinrich, D.S.P., A.C., C.E.P., M.-R.J., G.H.K., N.T., M.A.F., H.B. and A.J.H.
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I.J., G.T., U.T. and K. Stefansson are employees of deCODE Genetics. The other authors declare no competing financial interests.
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Bønnelykke, K., Matheson, M., Pers, T. et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet 45, 902–906 (2013). https://doi.org/10.1038/ng.2694
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DOI: https://doi.org/10.1038/ng.2694
