Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.,Nature Genetics

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Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.
Nature Genetics ( IF 30.8 ) Pub Date : 2017-Dec-01 , DOI: 10.1038/ng.3985
Manuel A Ferreira ₁ , Judith M Vonk ₂ , Hansjörg Baurecht ₃ , Ingo Marenholz _{4,

5} , Chao Tian ₆ , Joshua D Hoffman ₇ , Quinta Helmer ₈ , Annika Tillander ₉ , Vilhelmina Ullemar ₉ , Jenny van Dongen ₈ , Yi Lu ₉ , Franz Rüschendorf ₄ , Jorge Esparza-Gordillo _{4,

5} , Chris W Medway ₁₀ , Edward Mountjoy ₁₀ , Kimberley Burrows ₁₀ , Oliver Hummel ₄ , Sarah Grosche _{4,

5} , Ben M Brumpton _{10,

11,

12} , John S Witte ₁₃ , Jouke-Jan Hottenga ₈ , Gonneke Willemsen ₈ , Jie Zheng ₁₀ , Elke Rodríguez ₃ , Melanie Hotze ₃ , Andre Franke ₁₄ , Joana A Revez ₁ , Jonathan Beesley ₁ , Melanie C Matheson ₁₅ , Shyamali C Dharmage ₁₅ , Lisa M Bain ₁ , Lars G Fritsche ₁₁ , Maiken E Gabrielsen ₁₁ , Brunilda Balliu ₁₆ , , , , , Jonas B Nielsen _{17,

18} , Wei Zhou ₁₈ , Kristian Hveem _{11,

19} , Arnulf Langhammer ₁₉ , Oddgeir L Holmen ₁₁ , Mari Løset _{11,

20} , Gonçalo R Abecasis _{11,

21} , Cristen J Willer _{11,

17,

18,

21} , Andreas Arnold ₂₂ , Georg Homuth ₂₃ , Carsten O Schmidt ₂₄ , Philip J Thompson ₂₅ , Nicholas G Martin ₁ , David L Duffy ₁ , Natalija Novak ₂₆ , Holger Schulz _{27,

28} , Stefan Karrasch _{27,

28,

29} , Christian Gieger ₃₀ , Konstantin Strauch ₃₁ , Ronald B Melles ₃₂ , David A Hinds ₆ , Norbert Hübner ₄ , Stephan Weidinger ₃ , Patrik K E Magnusson ₉ , Rick Jansen ₃₃ , Eric Jorgenson ₃₂ , Young-Ae Lee _{4,

5} , Dorret I Boomsma ₈ , Catarina Almqvist _{9,

34} , Robert Karlsson ₉ , Gerard H Koppelman ₃₅ , Lavinia Paternoster ₁₀

Affiliation

Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Epidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.
Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany.
Research, 23andMe, Mountain View, California, USA.
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Department of Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, the Netherlands.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Thoracic Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany.
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany.
Institute for Respiratory Health, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
Department of Dermatology and Allergology, University Hospital Bonn, Bonn, Germany.
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany.
Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Research Unit of Molecular Epidemiology and Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10^-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

更新日期：2017-11-10

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