A sequence variant on 17q21 is associated with age at onset and severity of asthma

Eva Halapi; Daniel F Gudbjartsson; Gudrun M Jonsdottir; Unnur S Bjornsdottir; Gudmar Thorleifsson; Hafdis Helgadottir; Carolyn Williams; Gerard H Koppelman; Andrea Heinzmann; Hendrika Boezen; Aslaug Jonasdottir; Thorarinn Blondal; Sigurjon A Gudjonsson; Adalbjorg Jonasdottir; Theodora Thorlacius; Amanda P Henry; Janine Altmueller; Marcus Krueger; Hyoung Doo Shin; Soo-Taek Uh; Hyun Sub Cheong; Brynja Jonsdottir; Bjorn R Ludviksson; Dora Ludviksdottir; David Gislason; Choon-Sik Park; Klaus Deichmann; Philip J Thompson; Matthias Wjst; Ian P Hall; Dirkje S Postma; Thorarinn Gislason; Augustine Kong; Ingileif Jonsdottir; Unnur Thorsteinsdottir; Kari Stefansson

doi:10.1038/ejhg.2010.38

A sequence variant on 17q21 is associated with age at onset and severity of asthma

Eva Halapi
, Daniel F Gudbjartsson
, Gudrun M Jonsdottir
, Unnur S Bjornsdottir
, Gudmar Thorleifsson
, Hafdis Helgadottir
, Carolyn Williams
, Gerard H Koppelman
, Andrea Heinzmann
, Hendrika Boezen
, Aslaug Jonasdottir
, Thorarinn Blondal
, Sigurjon A Gudjonsson
, Adalbjorg Jonasdottir
, Theodora Thorlacius
, Amanda P Henry
, Janine Altmueller
, Marcus Krueger
, Hyoung Doo Shin
, Soo-Taek Uh

Hyun Sub Cheong, Brynja Jonsdottir, Bjorn R Ludviksson, Dora Ludviksdottir, David Gislason, Choon-Sik Park, Klaus Deichmann, Philip J Thompson, Matthias Wjst, Ian P Hall, Dirkje S Postma, Thorarinn Gislason, Augustine Kong, Ingileif Jonsdottir, Unnur Thorsteinsdottir^*, Kari Stefansson

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

128 Citations (Scopus)

Abstract

A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N=4917 cases N=34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR=1.51, P=6.89.10(-9)) and adolescence (age: 14-17 years OR=1.71, P=5.47.10(-9)). A weaker association was observed for onset between 6 and 13 years of age (OR=1.17, P=0.035), but none for adult-onset asthma (OR=1.07, P=0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P=0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n=743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.

Original language	English
Pages (from-to)	902-908
Number of pages	7
Journal	European Journal of Human Genetics
Volume	18
Issue number	8
DOIs	https://doi.org/10.1038/ejhg.2010.38
Publication status	Published - Aug-2010

Keywords

childhood asthma
single-nucleotide polymorphism
expression
ORMDL3
GSDMB
GENOME-WIDE ASSOCIATION
SUSCEPTIBILITY GENE
ORMDL3 EXPRESSION
RESEARCH-PROGRAM
ATOPIC DISEASES
POPULATION
CHILDHOOD
POLYMORPHISMS
FAMILIES
SEARCH

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Halapi, E., Gudbjartsson, D. F., Jonsdottir, G. M., Bjornsdottir, U. S., Thorleifsson, G., Helgadottir, H., Williams, C., Koppelman, G. H., Heinzmann, A., Boezen, H., Jonasdottir, A., Blondal, T., Gudjonsson, S. A., Jonasdottir, A., Thorlacius, T., Henry, A. P., Altmueller, J., Krueger, M., Shin, H. D., ... Stefansson, K. (2010). A sequence variant on 17q21 is associated with age at onset and severity of asthma. European Journal of Human Genetics, 18(8), 902-908. https://doi.org/10.1038/ejhg.2010.38

@article{8cc0c47f5dee41ae8b14b165bc166185,

title = "A sequence variant on 17q21 is associated with age at onset and severity of asthma",

abstract = "A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N=4917 cases N=34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR=1.51, P=6.89.10(-9)) and adolescence (age: 14-17 years OR=1.71, P=5.47.10(-9)). A weaker association was observed for onset between 6 and 13 years of age (OR=1.17, P=0.035), but none for adult-onset asthma (OR=1.07, P=0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P=0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n=743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.",

keywords = "childhood asthma, single-nucleotide polymorphism, expression, ORMDL3, GSDMB, GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY GENE, ORMDL3 EXPRESSION, RESEARCH-PROGRAM, ATOPIC DISEASES, POPULATION, CHILDHOOD, POLYMORPHISMS, FAMILIES, SEARCH",

author = "Eva Halapi and Gudbjartsson, \{Daniel F\} and Jonsdottir, \{Gudrun M\} and Bjornsdottir, \{Unnur S\} and Gudmar Thorleifsson and Hafdis Helgadottir and Carolyn Williams and Koppelman, \{Gerard H\} and Andrea Heinzmann and Hendrika Boezen and Aslaug Jonasdottir and Thorarinn Blondal and Gudjonsson, \{Sigurjon A\} and Adalbjorg Jonasdottir and Theodora Thorlacius and Henry, \{Amanda P\} and Janine Altmueller and Marcus Krueger and Shin, \{Hyoung Doo\} and Soo-Taek Uh and Cheong, \{Hyun Sub\} and Brynja Jonsdottir and Ludviksson, \{Bjorn R\} and Dora Ludviksdottir and David Gislason and Choon-Sik Park and Klaus Deichmann and Thompson, \{Philip J\} and Matthias Wjst and Hall, \{Ian P\} and Postma, \{Dirkje S\} and Thorarinn Gislason and Augustine Kong and Ingileif Jonsdottir and Unnur Thorsteinsdottir and Kari Stefansson",

year = "2010",

month = aug,

doi = "10.1038/ejhg.2010.38",

language = "English",

volume = "18",

pages = "902--908",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Nature Publishing Group",

number = "8",

}

Halapi, E, Gudbjartsson, DF, Jonsdottir, GM, Bjornsdottir, US, Thorleifsson, G, Helgadottir, H, Williams, C, Koppelman, GH, Heinzmann, A, Boezen, H, Jonasdottir, A, Blondal, T, Gudjonsson, SA, Jonasdottir, A, Thorlacius, T, Henry, AP, Altmueller, J, Krueger, M, Shin, HD, Uh, S-T, Cheong, HS, Jonsdottir, B, Ludviksson, BR, Ludviksdottir, D, Gislason, D, Park, C-S, Deichmann, K, Thompson, PJ, Wjst, M, Hall, IP, Postma, DS, Gislason, T, Kong, A, Jonsdottir, I, Thorsteinsdottir, U & Stefansson, K 2010, 'A sequence variant on 17q21 is associated with age at onset and severity of asthma', European Journal of Human Genetics, vol. 18, no. 8, pp. 902-908. https://doi.org/10.1038/ejhg.2010.38

TY - JOUR

T1 - A sequence variant on 17q21 is associated with age at onset and severity of asthma

AU - Halapi, Eva

AU - Gudbjartsson, Daniel F

AU - Jonsdottir, Gudrun M

AU - Bjornsdottir, Unnur S

AU - Thorleifsson, Gudmar

AU - Helgadottir, Hafdis

AU - Williams, Carolyn

AU - Koppelman, Gerard H

AU - Heinzmann, Andrea

AU - Boezen, Hendrika

AU - Jonasdottir, Aslaug

AU - Blondal, Thorarinn

AU - Gudjonsson, Sigurjon A

AU - Jonasdottir, Adalbjorg

AU - Thorlacius, Theodora

AU - Henry, Amanda P

AU - Altmueller, Janine

AU - Krueger, Marcus

AU - Shin, Hyoung Doo

AU - Uh, Soo-Taek

AU - Cheong, Hyun Sub

AU - Jonsdottir, Brynja

AU - Ludviksson, Bjorn R

AU - Ludviksdottir, Dora

AU - Gislason, David

AU - Park, Choon-Sik

AU - Deichmann, Klaus

AU - Thompson, Philip J

AU - Wjst, Matthias

AU - Hall, Ian P

AU - Postma, Dirkje S

AU - Gislason, Thorarinn

AU - Kong, Augustine

AU - Jonsdottir, Ingileif

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

PY - 2010/8

Y1 - 2010/8

N2 - A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N=4917 cases N=34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR=1.51, P=6.89.10(-9)) and adolescence (age: 14-17 years OR=1.71, P=5.47.10(-9)). A weaker association was observed for onset between 6 and 13 years of age (OR=1.17, P=0.035), but none for adult-onset asthma (OR=1.07, P=0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P=0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n=743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.

AB - A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N=4917 cases N=34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR=1.51, P=6.89.10(-9)) and adolescence (age: 14-17 years OR=1.71, P=5.47.10(-9)). A weaker association was observed for onset between 6 and 13 years of age (OR=1.17, P=0.035), but none for adult-onset asthma (OR=1.07, P=0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P=0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n=743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.

KW - childhood asthma

KW - single-nucleotide polymorphism

KW - expression

KW - ORMDL3

KW - GSDMB

KW - GENOME-WIDE ASSOCIATION

KW - SUSCEPTIBILITY GENE

KW - ORMDL3 EXPRESSION

KW - RESEARCH-PROGRAM

KW - ATOPIC DISEASES

KW - POPULATION

KW - CHILDHOOD

KW - POLYMORPHISMS

KW - FAMILIES

KW - SEARCH

U2 - 10.1038/ejhg.2010.38

DO - 10.1038/ejhg.2010.38

M3 - Article

C2 - 20372189

SN - 1018-4813

VL - 18

SP - 902

EP - 908

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 8

ER -

A sequence variant on 17q21 is associated with age at onset and severity of asthma

Abstract

Keywords

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