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Age-of-onset information helps identify 76 genetic variants associated with allergic disease
Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, h...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367489/ https://www.ncbi.nlm.nih.gov/pubmed/32603359 http://dx.doi.org/10.1371/journal.pgen.1008725 |
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author | Ferreira, Manuel A. R. Vonk, Judith M. Baurecht, Hansjörg Marenholz, Ingo Tian, Chao Hoffman, Joshua D. Helmer, Quinta Tillander, Annika Ullemar, Vilhelmina Lu, Yi Grosche, Sarah Rüschendorf, Franz Granell, Raquel Brumpton, Ben M. Fritsche, Lars G. Bhatta, Laxmi Gabrielsen, Maiken E. Nielsen, Jonas B. Zhou, Wei Hveem, Kristian Langhammer, Arnulf Holmen, Oddgeir L. Løset, Mari Abecasis, Gonçalo R. Willer, Cristen J. Emami, Nima C. Cavazos, Taylor B. Witte, John S. Szwajda, Agnieszka Hinds, David A. Hübner, Norbert Weidinger, Stephan Magnusson, Patrik KE Jorgenson, Eric Karlsson, Robert Paternoster, Lavinia Boomsma, Dorret I. Almqvist, Catarina Lee, Young-Ae Koppelman, Gerard H. |
author_facet | Ferreira, Manuel A. R. Vonk, Judith M. Baurecht, Hansjörg Marenholz, Ingo Tian, Chao Hoffman, Joshua D. Helmer, Quinta Tillander, Annika Ullemar, Vilhelmina Lu, Yi Grosche, Sarah Rüschendorf, Franz Granell, Raquel Brumpton, Ben M. Fritsche, Lars G. Bhatta, Laxmi Gabrielsen, Maiken E. Nielsen, Jonas B. Zhou, Wei Hveem, Kristian Langhammer, Arnulf Holmen, Oddgeir L. Løset, Mari Abecasis, Gonçalo R. Willer, Cristen J. Emami, Nima C. Cavazos, Taylor B. Witte, John S. Szwajda, Agnieszka Hinds, David A. Hübner, Norbert Weidinger, Stephan Magnusson, Patrik KE Jorgenson, Eric Karlsson, Robert Paternoster, Lavinia Boomsma, Dorret I. Almqvist, Catarina Lee, Young-Ae Koppelman, Gerard H. |
author_sort | Ferreira, Manuel A. R. |
collection | PubMed |
description | Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10(-8)) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (r(g) = -0.63, P = 4.5x10(-61)), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals. |
format | Online Article Text |
id | pubmed-7367489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73674892020-07-27 Age-of-onset information helps identify 76 genetic variants associated with allergic disease Ferreira, Manuel A. R. Vonk, Judith M. Baurecht, Hansjörg Marenholz, Ingo Tian, Chao Hoffman, Joshua D. Helmer, Quinta Tillander, Annika Ullemar, Vilhelmina Lu, Yi Grosche, Sarah Rüschendorf, Franz Granell, Raquel Brumpton, Ben M. Fritsche, Lars G. Bhatta, Laxmi Gabrielsen, Maiken E. Nielsen, Jonas B. Zhou, Wei Hveem, Kristian Langhammer, Arnulf Holmen, Oddgeir L. Løset, Mari Abecasis, Gonçalo R. Willer, Cristen J. Emami, Nima C. Cavazos, Taylor B. Witte, John S. Szwajda, Agnieszka Hinds, David A. Hübner, Norbert Weidinger, Stephan Magnusson, Patrik KE Jorgenson, Eric Karlsson, Robert Paternoster, Lavinia Boomsma, Dorret I. Almqvist, Catarina Lee, Young-Ae Koppelman, Gerard H. PLoS Genet Research Article Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10(-8)) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (r(g) = -0.63, P = 4.5x10(-61)), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals. Public Library of Science 2020-06-30 /pmc/articles/PMC7367489/ /pubmed/32603359 http://dx.doi.org/10.1371/journal.pgen.1008725 Text en © 2020 Ferreira et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ferreira, Manuel A. R. Vonk, Judith M. Baurecht, Hansjörg Marenholz, Ingo Tian, Chao Hoffman, Joshua D. Helmer, Quinta Tillander, Annika Ullemar, Vilhelmina Lu, Yi Grosche, Sarah Rüschendorf, Franz Granell, Raquel Brumpton, Ben M. Fritsche, Lars G. Bhatta, Laxmi Gabrielsen, Maiken E. Nielsen, Jonas B. Zhou, Wei Hveem, Kristian Langhammer, Arnulf Holmen, Oddgeir L. Løset, Mari Abecasis, Gonçalo R. Willer, Cristen J. Emami, Nima C. Cavazos, Taylor B. Witte, John S. Szwajda, Agnieszka Hinds, David A. Hübner, Norbert Weidinger, Stephan Magnusson, Patrik KE Jorgenson, Eric Karlsson, Robert Paternoster, Lavinia Boomsma, Dorret I. Almqvist, Catarina Lee, Young-Ae Koppelman, Gerard H. Age-of-onset information helps identify 76 genetic variants associated with allergic disease |
title | Age-of-onset information helps identify 76 genetic variants associated with allergic disease |
title_full | Age-of-onset information helps identify 76 genetic variants associated with allergic disease |
title_fullStr | Age-of-onset information helps identify 76 genetic variants associated with allergic disease |
title_full_unstemmed | Age-of-onset information helps identify 76 genetic variants associated with allergic disease |
title_short | Age-of-onset information helps identify 76 genetic variants associated with allergic disease |
title_sort | age-of-onset information helps identify 76 genetic variants associated with allergic disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367489/ https://www.ncbi.nlm.nih.gov/pubmed/32603359 http://dx.doi.org/10.1371/journal.pgen.1008725 |
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