Publication

Age-of-onset information helps identify 76 genetic variants associated with allergic disease

23andMe Res Team, Collaborators SHARE Study, Ferreira, M. A. R., Vonk, J. M., Baurecht, H., Marenholz, I., Tian, C., Hoffman, J. D., Helmer, Q., Tillander, A., Ullemar, V., Lu, Y., Grosche, S., Rueschendorf, F., Granell, R., Brumpton, B. M., Fritsche, L. G., Bhatta, L., Gabrielsen, M. E., Nielsen, J. B., Zhou, W., Hveem, K., Langhammer, A., Holmen, O. L., Loset, M., Abecasis, G. R., Willer, C. J., Emami, N. C., Cavazos, T. B., Witte, J. S., Szwajda, A., Hinds, D. A., Huebner, N., Weidinger, S., Magnusson, P. K. E., Jorgenson, E., Karlsson, R., Paternoster, L., Boomsma, D., Almqvist, C., Lee, Y-A. & Koppelman, G. H., Jun-2020, In : PLoS genetics. 16, 6, 30 p., e1008725.

Research output: Contribution to journalArticleAcademicpeer-review

APA

23andMe Res Team, Collaborators SHARE Study, Ferreira, M. A. R., Vonk, J. M., Baurecht, H., Marenholz, I., Tian, C., Hoffman, J. D., Helmer, Q., Tillander, A., Ullemar, V., Lu, Y., Grosche, S., Rueschendorf, F., Granell, R., Brumpton, B. M., Fritsche, L. G., Bhatta, L., Gabrielsen, M. E., ... Koppelman, G. H. (2020). Age-of-onset information helps identify 76 genetic variants associated with allergic disease. PLoS genetics, 16(6), [e1008725]. https://doi.org/10.1371/journal.pgen.1008725

Author

23andMe Res Team ; Collaborators SHARE Study ; Ferreira, Manuel A. R. ; Vonk, Judith M. ; Baurecht, Hansjoerg ; Marenholz, Ingo ; Tian, Chao ; Hoffman, Joshua D. ; Helmer, Quinta ; Tillander, Annika ; Ullemar, Vilhelmina ; Lu, Yi ; Grosche, Sarah ; Rueschendorf, 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. ; Loset, Mari ; Abecasis, Goncalo R. ; Willer, Cristen J. ; Emami, Nima C. ; Cavazos, Taylor B. ; Witte, John S. ; Szwajda, Agnieszka ; Hinds, David A. ; Huebner, Norbert ; Weidinger, Stephan ; Magnusson, Patrik K. E. ; Jorgenson, Eric ; Karlsson, Robert ; Paternoster, Lavinia ; Boomsma, Dorret ; Almqvist, Catarina ; Lee, Young-Ae ; Koppelman, Gerard H. / Age-of-onset information helps identify 76 genetic variants associated with allergic disease. In: PLoS genetics. 2020 ; Vol. 16, No. 6.

Harvard

23andMe Res Team, Collaborators SHARE Study, Ferreira, MAR, Vonk, JM, Baurecht, H, Marenholz, I, Tian, C, Hoffman, JD, Helmer, Q, Tillander, A, Ullemar, V, Lu, Y, Grosche, S, Rueschendorf, F, Granell, R, Brumpton, BM, Fritsche, LG, Bhatta, L, Gabrielsen, ME, Nielsen, JB, Zhou, W, Hveem, K, Langhammer, A, Holmen, OL, Loset, M, Abecasis, GR, Willer, CJ, Emami, NC, Cavazos, TB, Witte, JS, Szwajda, A, Hinds, DA, Huebner, N, Weidinger, S, Magnusson, PKE, Jorgenson, E, Karlsson, R, Paternoster, L, Boomsma, D, Almqvist, C, Lee, Y-A & Koppelman, GH 2020, 'Age-of-onset information helps identify 76 genetic variants associated with allergic disease', PLoS genetics, vol. 16, no. 6, e1008725. https://doi.org/10.1371/journal.pgen.1008725

Standard

Age-of-onset information helps identify 76 genetic variants associated with allergic disease. / 23andMe Res Team; Collaborators SHARE Study; Ferreira, Manuel A. R.; Vonk, Judith M.; Baurecht, Hansjoerg; Marenholz, Ingo; Tian, Chao; Hoffman, Joshua D.; Helmer, Quinta; Tillander, Annika; Ullemar, Vilhelmina; Lu, Yi; Grosche, Sarah; Rueschendorf, 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.; Loset, Mari; Abecasis, Goncalo R.; Willer, Cristen J.; Emami, Nima C.; Cavazos, Taylor B.; Witte, John S.; Szwajda, Agnieszka; Hinds, David A.; Huebner, Norbert; Weidinger, Stephan; Magnusson, Patrik K. E.; Jorgenson, Eric; Karlsson, Robert; Paternoster, Lavinia; Boomsma, Dorret; Almqvist, Catarina; Lee, Young-Ae; Koppelman, Gerard H.

In: PLoS genetics, Vol. 16, No. 6, e1008725, 06.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

23andMe Res Team, Collaborators SHARE Study, Ferreira MAR, Vonk JM, Baurecht H, Marenholz I et al. Age-of-onset information helps identify 76 genetic variants associated with allergic disease. PLoS genetics. 2020 Jun;16(6). e1008725. https://doi.org/10.1371/journal.pgen.1008725


BibTeX

@article{5d61eae6301545a68676107d6378adfc,
title = "Age-of-onset information helps identify 76 genetic variants associated with allergic disease",
abstract = "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<3×10-8) 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 (rg =-0.63, P = 4.5×10-61), 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.",
keywords = "GENOME-WIDE ASSOCIATION, ATOPIC-DERMATITIS, SUSCEPTIBILITY LOCI, T-CELLS, CD200 RECEPTOR, II RECEPTOR, RISK LOCI, HAY-FEVER, PKC-THETA, ASTHMA",
author = "{23andMe Res Team} and {Collaborators SHARE Study} and Ferreira, {Manuel A. R.} and Vonk, {Judith M.} and Hansjoerg Baurecht and Ingo Marenholz and Chao Tian and Hoffman, {Joshua D.} and Quinta Helmer and Annika Tillander and Vilhelmina Ullemar and Yi Lu and Sarah Grosche and Franz Rueschendorf and Raquel Granell and Brumpton, {Ben M.} and Fritsche, {Lars G.} and Laxmi Bhatta and Gabrielsen, {Maiken E.} and Nielsen, {Jonas B.} and Wei Zhou and Kristian Hveem and Arnulf Langhammer and Holmen, {Oddgeir L.} and Mari Loset and Abecasis, {Goncalo R.} and Willer, {Cristen J.} and Emami, {Nima C.} and Cavazos, {Taylor B.} and Witte, {John S.} and Agnieszka Szwajda and Hinds, {David A.} and Norbert Huebner and Stephan Weidinger and Magnusson, {Patrik K. E.} and Eric Jorgenson and Robert Karlsson and Lavinia Paternoster and Dorret Boomsma and Catarina Almqvist and Young-Ae Lee and Koppelman, {Gerard H.}",
year = "2020",
month = jun,
doi = "10.1371/journal.pgen.1008725",
language = "English",
volume = "16",
journal = "PLoS genetics",
issn = "1553-7390",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "6",

}

RIS

TY - JOUR

T1 - Age-of-onset information helps identify 76 genetic variants associated with allergic disease

AU - 23andMe Res Team

AU - Collaborators SHARE Study

AU - Ferreira, Manuel A. R.

AU - Vonk, Judith M.

AU - Baurecht, Hansjoerg

AU - Marenholz, Ingo

AU - Tian, Chao

AU - Hoffman, Joshua D.

AU - Helmer, Quinta

AU - Tillander, Annika

AU - Ullemar, Vilhelmina

AU - Lu, Yi

AU - Grosche, Sarah

AU - Rueschendorf, Franz

AU - Granell, Raquel

AU - Brumpton, Ben M.

AU - Fritsche, Lars G.

AU - Bhatta, Laxmi

AU - Gabrielsen, Maiken E.

AU - Nielsen, Jonas B.

AU - Zhou, Wei

AU - Hveem, Kristian

AU - Langhammer, Arnulf

AU - Holmen, Oddgeir L.

AU - Loset, Mari

AU - Abecasis, Goncalo R.

AU - Willer, Cristen J.

AU - Emami, Nima C.

AU - Cavazos, Taylor B.

AU - Witte, John S.

AU - Szwajda, Agnieszka

AU - Hinds, David A.

AU - Huebner, Norbert

AU - Weidinger, Stephan

AU - Magnusson, Patrik K. E.

AU - Jorgenson, Eric

AU - Karlsson, Robert

AU - Paternoster, Lavinia

AU - Boomsma, Dorret

AU - Almqvist, Catarina

AU - Lee, Young-Ae

AU - Koppelman, Gerard H.

PY - 2020/6

Y1 - 2020/6

N2 - 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<3×10-8) 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 (rg =-0.63, P = 4.5×10-61), 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.

AB - 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<3×10-8) 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 (rg =-0.63, P = 4.5×10-61), 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.

KW - GENOME-WIDE ASSOCIATION

KW - ATOPIC-DERMATITIS

KW - SUSCEPTIBILITY LOCI

KW - T-CELLS

KW - CD200 RECEPTOR

KW - II RECEPTOR

KW - RISK LOCI

KW - HAY-FEVER

KW - PKC-THETA

KW - ASTHMA

U2 - 10.1371/journal.pgen.1008725

DO - 10.1371/journal.pgen.1008725

M3 - Article

C2 - 32603359

VL - 16

JO - PLoS genetics

JF - PLoS genetics

SN - 1553-7390

IS - 6

M1 - e1008725

ER -

ID: 130031649