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Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct

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Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. / the 23 and Me Research Team; eQTLGen Consortium; BIOS Consortium.

In: American Journal of Human Genetics, Vol. 104, No. 4, 04.04.2019, p. 665-684.

Research output: Contribution to journalArticle

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the 23 and Me Research Team, eQTLGen Consortium & BIOS Consortium 2019, 'Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct', American Journal of Human Genetics, vol. 104, no. 4, pp. 665-684. https://doi.org/10.1016/j.ajhg.2019.02.022

APA

the 23 and Me Research Team, eQTLGen Consortium, & BIOS Consortium (2019). Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. American Journal of Human Genetics, 104(4), 665-684. https://doi.org/10.1016/j.ajhg.2019.02.022

Vancouver

the 23 and Me Research Team, eQTLGen Consortium, BIOS Consortium. Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. American Journal of Human Genetics. 2019 Apr 4;104(4):665-684. https://doi.org/10.1016/j.ajhg.2019.02.022

Author

the 23 and Me Research Team ; eQTLGen Consortium ; BIOS Consortium. / Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. In: American Journal of Human Genetics. 2019 ; Vol. 104, No. 4. pp. 665-684.

Bibtex

@article{d0293c902a004237b89407c0dc48b139,
title = "Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct",
abstract = "The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n = 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h 2 g = 25.6{\%}) than for AOA (onset at ages between 20 and 60 years; h 2 g = 10.6{\%}). The genetic correlation (r g ) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h 2 g = 5{\%}), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n = 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA- than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n = 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.",
keywords = "age, allergy, asthma, genetic, genome, GWAS, heritability, onset, overlap, risk",
author = "{the 23 and Me Research Team} and {eQTLGen Consortium} and {BIOS Consortium} and Ferreira, {Manuel A.R.} and Riddhima Mathur and Vonk, {Judith M.} and Agnieszka Szwajda and Ben Brumpton and Raquel Granell and Brew, {Bronwyn K.} and Vilhelmina Ullemar and Yi Lu and Yunxuan Jiang and Magnusson, {Patrik K.E.} and Robert Karlsson and Hinds, {David A.} and Lavinia Paternoster and Koppelman, {Gerard H.} and Catarina Almqvist",
year = "2019",
month = "4",
day = "4",
doi = "10.1016/j.ajhg.2019.02.022",
language = "English",
volume = "104",
pages = "665--684",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct

AU - the 23 and Me Research Team

AU - eQTLGen Consortium

AU - BIOS Consortium

AU - Ferreira, Manuel A.R.

AU - Mathur, Riddhima

AU - Vonk, Judith M.

AU - Szwajda, Agnieszka

AU - Brumpton, Ben

AU - Granell, Raquel

AU - Brew, Bronwyn K.

AU - Ullemar, Vilhelmina

AU - Lu, Yi

AU - Jiang, Yunxuan

AU - Magnusson, Patrik K.E.

AU - Karlsson, Robert

AU - Hinds, David A.

AU - Paternoster, Lavinia

AU - Koppelman, Gerard H.

AU - Almqvist, Catarina

PY - 2019/4/4

Y1 - 2019/4/4

N2 - The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n = 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h 2 g = 25.6%) than for AOA (onset at ages between 20 and 60 years; h 2 g = 10.6%). The genetic correlation (r g ) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h 2 g = 5%), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n = 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA- than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n = 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.

AB - The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n = 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h 2 g = 25.6%) than for AOA (onset at ages between 20 and 60 years; h 2 g = 10.6%). The genetic correlation (r g ) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h 2 g = 5%), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n = 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA- than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n = 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.

KW - age

KW - allergy

KW - asthma

KW - genetic

KW - genome

KW - GWAS

KW - heritability

KW - onset

KW - overlap

KW - risk

UR - http://www.scopus.com/inward/record.url?scp=85063686271&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2019.02.022

DO - 10.1016/j.ajhg.2019.02.022

M3 - Article

VL - 104

SP - 665

EP - 684

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 4

ER -