Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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29083406
TITLE
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.
ABSTRACT
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.
DATE PUBLISHED
2017 Oct 30
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/06/13
accepted 2017/10/06
entrez 2017/10/31 06:00
pubmed 2017/10/31 06:00
medline 2017/10/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ferreira MA Ferreira Manuel A MA Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Vonk JM Vonk Judith M JM Epidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.
Baurecht H Baurecht Hansjörg H Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Marenholz I Marenholz Ingo I Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany.
Tian C Tian Chao C Research, 23andMe, Mountain View, California, USA.
Hoffman JD Hoffman Joshua D JD Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Helmer Q Helmer Quinta Q Department of Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, the Netherlands.
Tillander A Tillander Annika A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ullemar V Ullemar Vilhelmina V Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
van Dongen J van Dongen Jenny J Department of Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, the Netherlands.
Lu Y Lu Yi Y Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Rüschendorf F Rüschendorf Franz F Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Esparza-Gordillo J Esparza-Gordillo Jorge J Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany.
Medway CW Medway Chris W CW MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Mountjoy E Mountjoy Edward E MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Burrows K Burrows Kimberley K MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Hummel O Hummel Oliver O Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Grosche S Grosche Sarah S Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany.
Brumpton BM Brumpton Ben M BM Department of Thoracic Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Witte JS Witte John S JS Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Hottenga JJ Hottenga Jouke-Jan JJ Department of Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, the Netherlands.
Willemsen G Willemsen Gonneke G Department of Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, the Netherlands.
Zheng J Zheng Jie J MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Rodríguez E Rodríguez Elke E Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Hotze M Hotze Melanie M Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Franke A Franke Andre A Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
Revez JA Revez Joana A JA Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Beesley J Beesley Jonathan J Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Matheson MC Matheson Melanie C MC Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
Dharmage SC Dharmage Shyamali C SC Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
Bain LM Bain Lisa M LM Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Fritsche LG Fritsche Lars G LG K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Gabrielsen ME Gabrielsen Maiken E ME K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Balliu B Balliu Brunilda B Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
23andMe Research Team
AAGC collaborators
BIOS consortium
LifeLines Cohort Study
Nielsen JB Nielsen Jonas B JB Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Zhou W Zhou Wei W Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Hveem K Hveem Kristian K HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Langhammer A Langhammer Arnulf A HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Holmen OL Holmen Oddgeir L OL K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Løset M Løset Mari M Department of Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Abecasis GR Abecasis Gonçalo R GR Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Willer CJ Willer Cristen J CJ Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Arnold A Arnold Andreas A Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany.
Homuth G Homuth Georg G Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
Schmidt CO Schmidt Carsten O CO Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany.
Thompson PJ Thompson Philip J PJ Institute for Respiratory Health, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
Martin NG Martin Nicholas G NG Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Duffy DL Duffy David L DL Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Novak N Novak Natalija N Department of Dermatology and Allergology, University Hospital Bonn, Bonn, Germany.
Schulz H Schulz Holger H Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany.
Karrasch S Karrasch Stefan S Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Gieger C Gieger Christian C Research Unit of Molecular Epidemiology and Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Strauch K Strauch Konstantin K Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Melles RB Melles Ronald B RB Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Hinds DA Hinds David A DA Research, 23andMe, Mountain View, California, USA.
Hübner N Hübner Norbert N Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Weidinger S Weidinger Stephan S Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Magnusson PKE Magnusson Patrik K E PKE Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Jansen R Jansen Rick R Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
Jorgenson E Jorgenson Eric E Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Lee YA Lee Young-Ae YA Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, the Netherlands.
Almqvist C Almqvist Catarina C Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Karlsson R Karlsson Robert R Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Koppelman GH Koppelman Gerard H GH 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.
Paternoster L Paternoster Lavinia L MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2017
MONTH: Oct
DAY: 30
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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