Cargando…

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

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2–4. To identify shared risk variants, we performed a genome-wide association study (GWAS, n=360,838) of a broad allergic disease phenotype that...

Descripción completa

Detalles Bibliográficos
Autores principales: Ferreira, Manuel A, Vonk, Judith M, Baurecht, Hansjörg, Marenholz, Ingo, Tian, Chao, Hoffman, Joshua D, Helmer, Quinta, Tillander, Annika, Ullemar, Vilhelmina, van Dongen, Jenny, Lu, Yi, Rüschendorf, Franz, Esparza-Gordillo, Jorge, Medway, Chris W, Mountjoy, Edward, Burrows, Kimberley, Hummel, Oliver, Grosche, Sarah, Brumpton, Ben M, Witte, John S, Hottenga, Jouke-Jan, Willemsen, Gonneke, Zheng, Jie, Rodríguez, Elke, Hotze, Melanie, Franke, Andre, Revez, Joana A, Beesley, Jonathan, Matheson, Melanie C, Dharmage, Shyamali C, Bain, Lisa M, Fritsche, Lars G, Gabrielsen, Maiken E, Balliu, Brunilda, Nielsen, Jonas B, Zhou, Wei, Hveem, Kristian, Langhammer, Arnulf, Holmen, Oddgeir L, Løset, Mari, Abecasis, Gonçalo R, Willer, Cristen J, Arnold, Andreas, Homuth, Georg, Schmidt, Carsten O, Thompson, Philip J, Martin, Nicholas G, Duffy, David L, Novak, Natalija, Schulz, Holger, Karrasch, Stefan, Gieger, Christian, Strauch, Konstantin, Melles, Ronald B, Hinds, David A, Hübner, Norbert, Weidinger, Stephan, Magnusson, Patrik KE, Jansen, Rick, Jorgenson, Eric, Lee, Young-Ae, Boomsma, Dorret I, Almqvist, Catarina, Karlsson, Robert, Koppelman, Gerard H, Paternoster, Lavinia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989923/
https://www.ncbi.nlm.nih.gov/pubmed/29083406
http://dx.doi.org/10.1038/ng.3985
_version_ 1783329540333895680
author Ferreira, Manuel A
Vonk, Judith M
Baurecht, Hansjörg
Marenholz, Ingo
Tian, Chao
Hoffman, Joshua D
Helmer, Quinta
Tillander, Annika
Ullemar, Vilhelmina
van Dongen, Jenny
Lu, Yi
Rüschendorf, Franz
Esparza-Gordillo, Jorge
Medway, Chris W
Mountjoy, Edward
Burrows, Kimberley
Hummel, Oliver
Grosche, Sarah
Brumpton, Ben M
Witte, John S
Hottenga, Jouke-Jan
Willemsen, Gonneke
Zheng, Jie
Rodríguez, Elke
Hotze, Melanie
Franke, Andre
Revez, Joana A
Beesley, Jonathan
Matheson, Melanie C
Dharmage, Shyamali C
Bain, Lisa M
Fritsche, Lars G
Gabrielsen, Maiken E
Balliu, Brunilda
Nielsen, Jonas B
Zhou, Wei
Hveem, Kristian
Langhammer, Arnulf
Holmen, Oddgeir L
Løset, Mari
Abecasis, Gonçalo R
Willer, Cristen J
Arnold, Andreas
Homuth, Georg
Schmidt, Carsten O
Thompson, Philip J
Martin, Nicholas G
Duffy, David L
Novak, Natalija
Schulz, Holger
Karrasch, Stefan
Gieger, Christian
Strauch, Konstantin
Melles, Ronald B
Hinds, David A
Hübner, Norbert
Weidinger, Stephan
Magnusson, Patrik KE
Jansen, Rick
Jorgenson, Eric
Lee, Young-Ae
Boomsma, Dorret I
Almqvist, Catarina
Karlsson, Robert
Koppelman, Gerard H
Paternoster, Lavinia
author_facet Ferreira, Manuel A
Vonk, Judith M
Baurecht, Hansjörg
Marenholz, Ingo
Tian, Chao
Hoffman, Joshua D
Helmer, Quinta
Tillander, Annika
Ullemar, Vilhelmina
van Dongen, Jenny
Lu, Yi
Rüschendorf, Franz
Esparza-Gordillo, Jorge
Medway, Chris W
Mountjoy, Edward
Burrows, Kimberley
Hummel, Oliver
Grosche, Sarah
Brumpton, Ben M
Witte, John S
Hottenga, Jouke-Jan
Willemsen, Gonneke
Zheng, Jie
Rodríguez, Elke
Hotze, Melanie
Franke, Andre
Revez, Joana A
Beesley, Jonathan
Matheson, Melanie C
Dharmage, Shyamali C
Bain, Lisa M
Fritsche, Lars G
Gabrielsen, Maiken E
Balliu, Brunilda
Nielsen, Jonas B
Zhou, Wei
Hveem, Kristian
Langhammer, Arnulf
Holmen, Oddgeir L
Løset, Mari
Abecasis, Gonçalo R
Willer, Cristen J
Arnold, Andreas
Homuth, Georg
Schmidt, Carsten O
Thompson, Philip J
Martin, Nicholas G
Duffy, David L
Novak, Natalija
Schulz, Holger
Karrasch, Stefan
Gieger, Christian
Strauch, Konstantin
Melles, Ronald B
Hinds, David A
Hübner, Norbert
Weidinger, Stephan
Magnusson, Patrik KE
Jansen, Rick
Jorgenson, Eric
Lee, Young-Ae
Boomsma, Dorret I
Almqvist, Catarina
Karlsson, Robert
Koppelman, Gerard H
Paternoster, Lavinia
author_sort Ferreira, Manuel A
collection PubMed
description Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2–4. 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<3x10(-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.
format Online
Article
Text
id pubmed-5989923
institution National Center for Biotechnology Information
language English
publishDate 2017
record_format MEDLINE/PubMed
spelling pubmed-59899232018-06-06 Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology Ferreira, Manuel A Vonk, Judith M Baurecht, Hansjörg Marenholz, Ingo Tian, Chao Hoffman, Joshua D Helmer, Quinta Tillander, Annika Ullemar, Vilhelmina van Dongen, Jenny Lu, Yi Rüschendorf, Franz Esparza-Gordillo, Jorge Medway, Chris W Mountjoy, Edward Burrows, Kimberley Hummel, Oliver Grosche, Sarah Brumpton, Ben M Witte, John S Hottenga, Jouke-Jan Willemsen, Gonneke Zheng, Jie Rodríguez, Elke Hotze, Melanie Franke, Andre Revez, Joana A Beesley, Jonathan Matheson, Melanie C Dharmage, Shyamali C Bain, Lisa M Fritsche, Lars G Gabrielsen, Maiken E Balliu, Brunilda Nielsen, Jonas B Zhou, Wei Hveem, Kristian Langhammer, Arnulf Holmen, Oddgeir L Løset, Mari Abecasis, Gonçalo R Willer, Cristen J Arnold, Andreas Homuth, Georg Schmidt, Carsten O Thompson, Philip J Martin, Nicholas G Duffy, David L Novak, Natalija Schulz, Holger Karrasch, Stefan Gieger, Christian Strauch, Konstantin Melles, Ronald B Hinds, David A Hübner, Norbert Weidinger, Stephan Magnusson, Patrik KE Jansen, Rick Jorgenson, Eric Lee, Young-Ae Boomsma, Dorret I Almqvist, Catarina Karlsson, Robert Koppelman, Gerard H Paternoster, Lavinia Nat Genet Article Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2–4. 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<3x10(-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. 2017-10-30 2017-12 /pmc/articles/PMC5989923/ /pubmed/29083406 http://dx.doi.org/10.1038/ng.3985 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ferreira, Manuel A
Vonk, Judith M
Baurecht, Hansjörg
Marenholz, Ingo
Tian, Chao
Hoffman, Joshua D
Helmer, Quinta
Tillander, Annika
Ullemar, Vilhelmina
van Dongen, Jenny
Lu, Yi
Rüschendorf, Franz
Esparza-Gordillo, Jorge
Medway, Chris W
Mountjoy, Edward
Burrows, Kimberley
Hummel, Oliver
Grosche, Sarah
Brumpton, Ben M
Witte, John S
Hottenga, Jouke-Jan
Willemsen, Gonneke
Zheng, Jie
Rodríguez, Elke
Hotze, Melanie
Franke, Andre
Revez, Joana A
Beesley, Jonathan
Matheson, Melanie C
Dharmage, Shyamali C
Bain, Lisa M
Fritsche, Lars G
Gabrielsen, Maiken E
Balliu, Brunilda
Nielsen, Jonas B
Zhou, Wei
Hveem, Kristian
Langhammer, Arnulf
Holmen, Oddgeir L
Løset, Mari
Abecasis, Gonçalo R
Willer, Cristen J
Arnold, Andreas
Homuth, Georg
Schmidt, Carsten O
Thompson, Philip J
Martin, Nicholas G
Duffy, David L
Novak, Natalija
Schulz, Holger
Karrasch, Stefan
Gieger, Christian
Strauch, Konstantin
Melles, Ronald B
Hinds, David A
Hübner, Norbert
Weidinger, Stephan
Magnusson, Patrik KE
Jansen, Rick
Jorgenson, Eric
Lee, Young-Ae
Boomsma, Dorret I
Almqvist, Catarina
Karlsson, Robert
Koppelman, Gerard H
Paternoster, Lavinia
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
title Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
title_full Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
title_fullStr Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
title_full_unstemmed Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
title_short Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
title_sort shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989923/
https://www.ncbi.nlm.nih.gov/pubmed/29083406
http://dx.doi.org/10.1038/ng.3985
work_keys_str_mv AT ferreiramanuela sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT vonkjudithm sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT baurechthansjorg sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT marenholzingo sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT tianchao sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT hoffmanjoshuad sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT helmerquinta sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT tillanderannika sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT ullemarvilhelmina sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT vandongenjenny sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT luyi sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT ruschendorffranz sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT esparzagordillojorge sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT medwaychrisw sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT mountjoyedward sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT burrowskimberley sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT hummeloliver sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT groschesarah sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT brumptonbenm sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT wittejohns sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT hottengajoukejan sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT willemsengonneke sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT zhengjie sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT rodriguezelke sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT hotzemelanie sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT frankeandre sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT revezjoanaa sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT beesleyjonathan sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT mathesonmelaniec sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT dharmageshyamalic sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT bainlisam sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT fritschelarsg sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT gabrielsenmaikene sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT balliubrunilda sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT nielsenjonasb sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT zhouwei sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT hveemkristian sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT langhammerarnulf sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT holmenoddgeirl sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT løsetmari sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT abecasisgoncalor sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT willercristenj sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT arnoldandreas sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT homuthgeorg sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT schmidtcarsteno sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT thompsonphilipj sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT martinnicholasg sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT duffydavidl sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT novaknatalija sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT schulzholger sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT karraschstefan sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT giegerchristian sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT strauchkonstantin sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT mellesronaldb sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT hindsdavida sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT hubnernorbert sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT weidingerstephan sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT magnussonpatrikke sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT jansenrick sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT jorgensoneric sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT leeyoungae sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT boomsmadorreti sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT almqvistcatarina sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT karlssonrobert sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT koppelmangerardh sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology
AT paternosterlavinia sharedgeneticoriginofasthmahayfeverandeczemaelucidatesallergicdiseasebiology