Mechanisms of allergy/immunologyShared genetic variants suggest common pathways in allergy and autoimmune diseases
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Section snippets
Study group
To obtain the largest possible GWAS data set for allergy, we meta-analyzed results from 2 recent GWASs on self-reported allergy9 and sensitization,10 including approximately 2.2 million directly genotyped and imputed single nucleotide polymorphisms (SNPs), by using a fixed-effects model. The self-reported allergy data set comprised 23,335 patients with self-reported allergy for cat, dust mite, and/or pollen allergy and 26,311 control subjects without symptoms. The allergic sensitization data
Allergy meta-analysis
Using the joint meta-analysis on combined data from allergic sensitization and self-reported allergy, we increased the number of allergy-associated SNPs compared with the previous GWAS (see Fig E2 in this article's Online Repository at www.jacionline.org), resulting in a total number of 19 genome-wide significant loci (see Fig E3 in this article's Online Repository at www.jacionline.org). One of these, rs11122898 near ANAPC1/MERKT (P = 1.9e-8), has not previously been associated with allergy or
Discussion
Our study demonstrated substantial commonalities between allergy and autoimmune diseases in terms of susceptibility loci, genetic pathways, and genomic regulatory sites (DHS). This overlap in genetic mechanisms seemed to be a general phenomenon for allergy and autoimmune diseases and distinct from other diseases. Our study identifies a substantial number of novel overlapping loci for allergy and autoimmune diseases suggesting both shared (increasing risk of both autoimmune and allergic
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2021, Mayo Clinic ProceedingsCitation Excerpt :Enhanced long-term risk of autoimmune disorders in patients with ADs is supported by novel findings from meta-analyses of 2 large genome-wide association studies in patients with ADs that were correlated with genome-wide association study data on autoimmune disorders.10 This study unraveled shared genetic loci and molecular pathways, importantly those involving transcription factors, transcription cofactors, and regulators relevant to ADs and autoimmune disorders.10 These genetic loci either had the same (converging or shared) or opposite (diverging) directional effects with respect to potentially enhancing risk/co-occurrence of ADs and autoimmune disorders or enhancing the risk of one and having a protective effect on the other, respectively.10
Disclosure of potential conflict of interest: E. Kreiner is employed at Novo Nordisk A/S. A. Simpson has received a grant from the Medical Research Council. J. Y. Tung is employed by and receives stock/stock options from 23andMe. G. H. Koppelman has received grants from the Netherlands Lung Foundation, Stichting Astma Bestrijding, Ubbo Emmius Foundation, and TEVA, The Netherlands. D. S. Postma has consultant arrangements with Astra Zeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Takeda, and TEVA and has received grants from AstraZeneca, Chiesi, Genentech, GlaxoSmithKline, and Roche. C. E. Pennell has received grants from the National Health Medical Research Council, Telethon, and Telethon-Perth Children's Hospital Research Fund; is employed by the University of Western Australia; and has received travel support for invited presentations from Raine Study Core Funds, Haematology Association of Australia, Global Obstetric Update, March of Dimes and Burrows Wellcome. A. Custovic has received personal fees from Novartis, Regeneron/Sanofi, ALK-Abelló, Bayer, and Thermo Fisher. M. A. Ferreira has received a grant from the National Health Medical Research Council of Australia (Project Grant 613627). J. Henderson has received grants from the Medical Research Council, Wellcome, and 23andMe. D. Hinds has received a grant from the National Heart, Lung, and Blood Institute (grant 1R43HL115873-01) and is employed by and has received stock/stock options from 23andMe. H. Bisgaard has received grants from the Danish Ministry of Health, the Lundbeck Foundation, and the Danish Strategic Research Foundation and has consultant arrangements with Chiesi Pharmaceuticals and Boehringer Ingelheim. K. Bønnelykke has received grants from the Danish Ministry of Health, the Lundbeck Foundation, and the Danish Strategic Research Foundation. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.