|
PMID |
|
|
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 |
|
|
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 |
|
COMMENTS AND CORRECTIONS |
|
|
GRANTS |
|
|
GENERAL NOTE |
|
|
KEYWORDS |
|
|
MESH HEADINGS |
|
|
SUPPLEMENTARY MESH |
|
|
GENE SYMBOLS |
|
|
CHEMICALS |
|
|
OTHER ID's |
|
|
|