Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization (original) (raw)

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References

1. Johansson, S.G. et al. Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J. Allergy Clin. Immunol. 113, 832–836 (2004).
   Article CAS PubMed Google Scholar
2. Anderson, G.P. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 372, 1107–1119 (2008).
   Article PubMed Google Scholar
3. Los, H., Postmus, P.E. & Boomsma, D.I. Asthma genetics and intermediate phenotypes: a review from twin studies. Twin Res. 4, 81–93 (2001).
   Article CAS PubMed Google Scholar
4. Thomsen, S.F., Ulrik, C.S., Kyvik, K.O., Ferreira, M.A. & Backer, V. Multivariate genetic analysis of atopy phenotypes in a selected sample of twins. Clin. Exp. Allergy 36, 1382–1390 (2006).
   Article CAS PubMed Google Scholar
5. Thomsen, S.F., van der Sluis, S., Kyvik, K.O. & Backer, V. A study of asthma severity in adult twins. Clin. Respir. J. 6, 228–237 (2012).
   Article PubMed Google Scholar
6. Vercelli, D. Discovering susceptibility genes for asthma and allergy. Nat. Rev. Immunol. 8, 169–182 (2008).
   Article CAS PubMed Google Scholar
7. Ramasamy, A. et al. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J. Allergy Clin. Immunol. 128, 996–1005 (2011).
   Article CAS PubMed Google Scholar
8. Hinds, D.A. et al. A meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Nat. Genet. published online; 10.1035/ng.2686 (30 June 2013).
9. Zeller, T. et al. Genetics and beyond—the transcriptome of human monocytes and disease susceptibility. PLoS ONE 5, e10693 (2010).
   Article PubMed PubMed Central Google Scholar
10. Adhikary, S. & Eilers, M. Transcriptional regulation and transformation by Myc proteins. Nat. Rev. Mol. Cell Biol. 6, 635–645 (2005).
    Article CAS PubMed Google Scholar
11. Huppi, K. et al. The identification of microRNAs in a genomically unstable region of human chromosome 8q24. Mol. Cancer Res. 6, 212–221 (2008).
    Article CAS PubMed Google Scholar
12. Beck-Engeser, G.B. et al. _Pvt1_-encoded microRNAs in oncogenesis. Retrovirology 5, 4 (2008).
    Article PubMed PubMed Central Google Scholar
13. Sawcer, S. et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476, 214–219 (2011).
    CAS PubMed PubMed Central Google Scholar
14. Esparza-Gordillo, J. et al. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat. Genet. 41, 596–601 (2009).
    Article CAS PubMed Google Scholar
15. Ferreira, M.A. et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 378, 1006–1014 (2011).
    CAS PubMed PubMed Central Google Scholar
16. Anderson, C.A. et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat. Genet. 43, 246–252 (2011).
    Article CAS PubMed PubMed Central Google Scholar
17. Barrett, J.C. et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat. Genet. 40, 955–962 (2008).
    Article CAS PubMed PubMed Central Google Scholar
18. Kormann, M.S. et al. Toll-like receptor heterodimer variants protect from childhood asthma. J. Allergy Clin. Immunol. 122, 86–92 (2008).
    Article CAS PubMed Google Scholar
19. Lazarus, R. et al. TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples. Am. J. Respir. Crit. Care Med. 170, 594–600 (2004).
    Article PubMed Google Scholar
20. Reijmerink, N.E. et al. Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy. Eur. Respir. J. 38, 833–840 (2011).
    Article CAS PubMed Google Scholar
21. Tesse, R., Pandey, R.C. & Kabesch, M. Genetic variations in Toll-like receptor pathway genes influence asthma and atopy. Allergy 66, 307–316 (2011).
    Article CAS PubMed Google Scholar
22. Potaczek, D.P. & Kabesch, M. Current concepts of IgE regulation and impact of genetic determinants. Clin. Exp. Allergy 42, 852–871 (2012).
    Article CAS PubMed Google Scholar
23. Gudbjartsson, D.F. et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat. Genet. 41, 342–347 (2009).
    Article CAS PubMed Google Scholar
24. Savenije, O.E. et al. Interleukin-1 receptor–like 1 polymorphisms are associated with serum IL1RL1-a, eosinophils, and asthma in childhood. J. Allergy Clin. Immunol. 127, 750–756 (2011).
    Article CAS PubMed Google Scholar
25. Ichii, H. et al. Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells. Nat. Immunol. 3, 558–563 (2002).
    Article CAS PubMed Google Scholar
26. Christensen, U. et al. Family based association analysis of the IL2 and IL15 genes in allergic disorders. Eur. J. Hum. Genet. 14, 227–235 (2006).
    Article CAS PubMed Google Scholar
27. Howell, W.M. & Holgate, S.T. HLA genetics and allergic disease. Thorax 50, 815–818 (1995).
    Article CAS PubMed PubMed Central Google Scholar
28. Franke, A. et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42, 1118–1125 (2010).
    Article CAS PubMed PubMed Central Google Scholar
29. Martin, A.M. et al. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc. Natl. Acad. Sci. USA 101, 4180–4185 (2004).
    Article CAS PubMed PubMed Central Google Scholar
30. Strange, A. et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat. Genet. 42, 985–990 (2010).
    Article CAS PubMed PubMed Central Google Scholar
31. Segrè, A.V., Groop, L., Mootha, V.K., Daly, M.J. & Altshuler, D. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet. 6, e1001058 (2010).
    Article PubMed PubMed Central Google Scholar
32. Raychaudhuri, S. et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5, e1000534 (2009).
    Article PubMed PubMed Central Google Scholar
33. Moffatt, M.F. et al. A large-scale, consortium-based genomewide association study of asthma. N. Engl. J. Med. 363, 1211–1221 (2010).
    Article CAS PubMed PubMed Central Google Scholar
34. Paternoster, L. et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat. Genet. 44, 187–192 (2012).
    Article CAS Google Scholar
35. Rabin, R.L. & Levinson, A.I. The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature. Clin. Exp. Immunol. 153, 19–30 (2008).
    Article CAS PubMed PubMed Central Google Scholar
36. Pruim, R.J. et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26, 2336–2337 (2010).
    Article CAS PubMed PubMed Central Google Scholar
37. Rathmann, W. et al. Incidence of type 2 diabetes in the elderly German population and the effect of clinical and lifestyle risk factors: KORA S4/F4 cohort study. Diabet. Med. 26, 1212–1219 (2009).
    Article CAS PubMed Google Scholar
38. Mehta, D. et al. Impact of common regulatory single-nucleotide variants on gene expression profiles in whole blood. Eur. J. Hum. Genet. 21, 48–54 (2013).
    Article CAS PubMed Google Scholar
39. Emilsson, V. et al. Genetics of gene expression and its effect on disease. Nature 452, 423–428 (2008).
    CAS PubMed Google Scholar
40. Fairfax, B.P. et al. Genetics of gene expression in primary immune cells identifies cell type–specific master regulators and roles of HLA alleles. Nat. Genet. 44, 502–510 (2012).
    Article CAS PubMed PubMed Central Google Scholar
41. Du, P., Kibbe, W.A. & Lin, S.M. lumi: a pipeline for processing Illumina microarray. Bioinformatics 24, 1547–1548 (2008).
    Article CAS PubMed Google Scholar
42. Shabalin, A.A. Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics 28, 1353–1358 (2012).
    Article CAS PubMed PubMed Central Google Scholar
43. Raychaudhuri, S. VIZ-GRAIL: visualizing functional connections across disease loci. Bioinformatics 27, 1589–1590 (2011).
    Article CAS PubMed PubMed Central Google Scholar

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Acknowledgements

A full list of acknowledgments for each study is given in the Supplementary Note.

Author information

Author notes

1. Klaus Bønnelykke, Melanie C Matheson, Tune H Pers and Gerard H Koppelman: These authors contributed equally to this work.
2. Manuel A Ferreira, Hans Bisgaard and A John Henderson: These authors jointly directed this work.

Authors and Affiliations

1. COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, Denmark
   Klaus Bønnelykke, Eskil Kreiner-Møller & Hans Bisgaard
2. Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia
   Melanie C Matheson & Shyamali C Dharmage
3. Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark
   Tune H Pers & Ramneek Gupta
4. Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA
   Tune H Pers & Joel N Hirschhorn
5. Center for Basic and Translational Obesity Research, Children's Hospital, Boston, Massachusetts, USA
   Tune H Pers
6. Broad Institute, Cambridge, Massachusetts, USA
   Tune H Pers & Joel N Hirschhorn
7. School of Social and Community Medicine, University of Bristol, Bristol, UK
   Raquel Granell, Beate St Pourcain, Susan M Ring, Wendy L McArdle, John P Kemp, Nicholas Timpson & A John Henderson
8. Division of Population Health Sciences & Education, St. George's, University of London, London, UK
   David P Strachan & Wendy L McArdle
9. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
   Alexessander Couto Alves, Lachlan Coin & Paul Elliot
10. Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, Denmark
    Allan Linneberg & Lise L Husemoen
11. Manchester Academic Health Science Centre, University of Manchester, University Hospital of South Manchester National Health Service (NHS) Foundation Trust, Manchester, UK
    John A Curtin, Angela Simpson & Adnan Custovic
12. School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, Australia
    Nicole M Warrington & Craig E Pennell
13. Institute of Epidemiology I, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
    Marie Standl, Carla M T Tiesler, Elisabeth Thiering & Joachim Heinrich
14. Department of Epidemiology, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Marjan Kerkhof
15. deCODE Genetics, Reykjavik, Iceland
    Ingileif Jonsdottir, Gudmar Thorleifsson, Unnur Thorsteinsdottir & Kari Stefansson
16. University of Iceland, Reykjavik, Iceland
    Ingileif Jonsdottir, Unnur Thorsteinsdottir & Kari Stefansson
17. Department of Pediatrics, General Hospital Dr. Josip Bencevic Slavonski Brod, University of Osijek, Osijek, Croatia
    Blazenka K Bukvic & Mario Blekic
18. Institute of Health Sciences, University of Oulu, Oulu, Finland
    Marika Kaakinen & Marjo-Riitta Jarvelin
19. Biocenter Oulu, University of Oulu, Oulu, Finland
    Marika Kaakinen & Marjo-Riitta Jarvelin
20. Center for Applied Genomics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Patrick Sleimann & Hakon Hakonarsson
21. Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Patrick Sleimann & Hakon Hakonarsson
22. Institute of Human Genetics, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
    Katharina Schramm
23. Lung Institute of Western Australia, The University of Western Australia, Perth, Western Australia, Australia
    Svetlana Baltic, Loren Price & Philip J Thompson
24. Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Perth, Western Australia, Australia
    Svetlana Baltic, Loren Price & Philip J Thompson
25. PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia, Australia
    Jennie Hui
26. School of Population Health, The University of Western Australia, Nedlands, Western Australia, Australia
    Jennie Hui
27. School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia
    Jennie Hui
28. Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
    Jennie Hui & Alan James
29. School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
    Eugene H Walters
30. Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    David L Duffy, Clara S Tang, Grant W Montgomery & Manuel A Ferreira
31. School of Science and Health, University of Western Sydney, Penrith, New South Wales, Australia
    Graham Jones
32. Respiratory Medicine, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
    Colin F Robertson
33. Department of Environmental Health, National Institute for Health and Welfare (THL), Kuopio, Finland
    Juha Pekkanen
34. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
    Juha Pekkanen
35. Department of Clinical Sciences, Obstetrics and Gynecology, Institute of Clinical Medicine, University of Oulu, Oulu, Finland
    Anna-Liisa Hartikainen
36. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
    Christian Herder
37. School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia
    Alan James
38. Department of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Nedlands, Western Australia, Australia
    Alan James
39. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
    Melanie Waldenberger
40. Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Victoria, Australia
    Michael J Abramson
41. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Benjamin P Fairfax & Julian C Knight
42. Telethon Institute for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia
    Patrick Holt
43. Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia
    Patrick Holt
44. Queensland Children's Medical Research Institute, University of Queensland, World Health Organization (WHO) Collaborating Centre for Research on Children's Environmental Health, Brisbane, Queensland, Australia
    Peter Sly
45. Division of Genetics, Children's Hospital, Boston, Massachusetts, USA
    Joel N Hirschhorn
46. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    Joel N Hirschhorn
47. Department of Dermatology, Allergology and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
    Stephan Weidinger
48. Department of Pulmonology, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Dirkje S Postma
49. Department of Epidemiology and Biostatistics, School of Public Health, Medical Research Council–Health Protection Agency (MRC-HPA) Centre for Environment and Health, Imperial College London, London, UK
    Marjo-Riitta Jarvelin
50. National Institute of Health and Welfare, Oulu, Finland
    Marjo-Riitta Jarvelin
51. Unit of Primary Care, Oulu University Hospital, Oulu, Finland
    Marjo-Riitta Jarvelin
52. Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Gerard H Koppelman

Authors

1. Klaus Bønnelykke
2. Melanie C Matheson
3. Tune H Pers
4. Raquel Granell
5. David P Strachan
6. Alexessander Couto Alves
7. Allan Linneberg
8. John A Curtin
9. Nicole M Warrington
10. Marie Standl
11. Marjan Kerkhof
12. Ingileif Jonsdottir
13. Blazenka K Bukvic
14. Marika Kaakinen
15. Patrick Sleimann
16. Gudmar Thorleifsson
17. Unnur Thorsteinsdottir
18. Katharina Schramm
19. Svetlana Baltic
20. Eskil Kreiner-Møller
21. Angela Simpson
22. Beate St Pourcain
23. Lachlan Coin
24. Jennie Hui
25. Eugene H Walters
26. Carla M T Tiesler
27. David L Duffy
28. Graham Jones
29. Susan M Ring
30. Wendy L McArdle
31. Loren Price
32. Colin F Robertson
33. Juha Pekkanen
34. Clara S Tang
35. Elisabeth Thiering
36. Grant W Montgomery
37. Anna-Liisa Hartikainen
38. Shyamali C Dharmage
39. Lise L Husemoen
40. Christian Herder
41. John P Kemp
42. Paul Elliot
43. Alan James
44. Melanie Waldenberger
45. Michael J Abramson
46. Benjamin P Fairfax
47. Julian C Knight
48. Ramneek Gupta
49. Philip J Thompson
50. Patrick Holt
51. Peter Sly
52. Joel N Hirschhorn
53. Mario Blekic
54. Stephan Weidinger
55. Kari Stefansson
56. Joachim Heinrich
57. Dirkje S Postma
58. Adnan Custovic
59. Craig E Pennell
60. Marjo-Riitta Jarvelin
61. Gerard H Koppelman
62. Nicholas Timpson
63. Manuel A Ferreira
64. Hans Bisgaard

Consortia

Australian Asthma Genetics Consortium (AAGC)

the EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium

• A John Henderson

Contributions

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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Correspondence toKlaus Bønnelykke.

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Competing interests

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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• Received: 29 October 2012
• Accepted: 10 June 2013
• Published: 30 June 2013
• Issue date: August 2013
• DOI: https://doi.org/10.1038/ng.2694