FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses

Research output: Contribution to journal › Journal article › Research › peer-review

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FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses. / Ahluwalia, Tarunveer S.; Eliasen, Anders U.; Sevelsted, Astrid; Pedersen, Casper-Emil T.; Stokholm, Jakob; Chawes, Bo; Bork-Jensen, Jette; Grarup, Niels; Pedersen, Oluf; Hansen, Torben; Linneberg, Allan; Sharma, Amitabh; Weiss, Scott T.; Evans, Michael D.; Jackson, Daniel J.; Morin, Andreanne; Krogfelt, Karen A.; Schjørring, Susanne; Mortensen, Preben B.; Hougaard, David M.; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Mors, Ole; Nordentoft, Merete; Børglum, Anders D.; Werge, Thomas; Agerbo, Esben; Gern, James E.; Lemanske, Robert F.; Ober, Carole; Pedersen, Anders G.; Bisgaard, Hans; Bønnelykke, Klaus.

In: Nature Communications, Vol. 11, 6398, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ahluwalia, TS, Eliasen, AU, Sevelsted, A, Pedersen, C-ET, Stokholm, J, Chawes, B, Bork-Jensen, J, Grarup, N, Pedersen, O, Hansen, T, Linneberg, A, Sharma, A, Weiss, ST, Evans, MD, Jackson, DJ, Morin, A, Krogfelt, KA, Schjørring, S, Mortensen, PB, Hougaard, DM, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Mors, O, Nordentoft, M, Børglum, AD, Werge, T, Agerbo, E, Gern, JE, Lemanske, RF, Ober, C, Pedersen, AG, Bisgaard, H & Bønnelykke, K 2020, 'FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses', Nature Communications, vol. 11, 6398. https://doi.org/10.1038/s41467-020-19814-6

APA

Ahluwalia, T. S., Eliasen, A. U., Sevelsted, A., Pedersen, C-E. T., Stokholm, J., Chawes, B., Bork-Jensen, J., Grarup, N., Pedersen, O., Hansen, T., Linneberg, A., Sharma, A., Weiss, S. T., Evans, M. D., Jackson, D. J., Morin, A., Krogfelt, K. A., Schjørring, S., Mortensen, P. B., ... Bønnelykke, K. (2020). FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses. Nature Communications, 11, [6398]. https://doi.org/10.1038/s41467-020-19814-6

Vancouver

Ahluwalia TS, Eliasen AU, Sevelsted A, Pedersen C-ET, Stokholm J, Chawes B et al. FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses. Nature Communications. 2020;11. 6398. https://doi.org/10.1038/s41467-020-19814-6

Author

Ahluwalia, Tarunveer S. ; Eliasen, Anders U. ; Sevelsted, Astrid ; Pedersen, Casper-Emil T. ; Stokholm, Jakob ; Chawes, Bo ; Bork-Jensen, Jette ; Grarup, Niels ; Pedersen, Oluf ; Hansen, Torben ; Linneberg, Allan ; Sharma, Amitabh ; Weiss, Scott T. ; Evans, Michael D. ; Jackson, Daniel J. ; Morin, Andreanne ; Krogfelt, Karen A. ; Schjørring, Susanne ; Mortensen, Preben B. ; Hougaard, David M. ; Bybjerg-Grauholm, Jonas ; Bækvad-Hansen, Marie ; Mors, Ole ; Nordentoft, Merete ; Børglum, Anders D. ; Werge, Thomas ; Agerbo, Esben ; Gern, James E. ; Lemanske, Robert F. ; Ober, Carole ; Pedersen, Anders G. ; Bisgaard, Hans ; Bønnelykke, Klaus. / FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses. In: Nature Communications. 2020 ; Vol. 11.

Bibtex

@article{0e7ebf9aea314b1fa5a785917d95f192,
title = "FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses",
abstract = "Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises 2866 children experiencing severe asthma exacerbation between ages 2 and 6 years, and 65,415 non-asthmatic controls, and we replicate findings in 918 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohorts. We identify rs281379 near FUT2/MAMSTR on chromosome 19 as a novel risk locus (OR = 1.18 (95% CI = 1.11–1.25), Pdiscovery = 2.6 × 10−9) as well as a biologically plausible interaction between functional variants in FUT2 and ABO. We further discover and replicate a potential causal mechanism behind this interaction related to S. pneumoniae respiratory illnesses. These results suggest a novel mechanism of early childhood asthma and demonstrates the importance of phenotype-specificity for discovery of asthma genes and epistasis.",
author = "Ahluwalia, {Tarunveer S.} and Eliasen, {Anders U.} and Astrid Sevelsted and Pedersen, {Casper-Emil T.} and Jakob Stokholm and Bo Chawes and Jette Bork-Jensen and Niels Grarup and Oluf Pedersen and Torben Hansen and Allan Linneberg and Amitabh Sharma and Weiss, {Scott T.} and Evans, {Michael D.} and Jackson, {Daniel J.} and Andreanne Morin and Krogfelt, {Karen A.} and Susanne Schj{\o}rring and Mortensen, {Preben B.} and Hougaard, {David M.} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Ole Mors and Merete Nordentoft and B{\o}rglum, {Anders D.} and Thomas Werge and Esben Agerbo and Gern, {James E.} and Lemanske, {Robert F.} and Carole Ober and Pedersen, {Anders G.} and Hans Bisgaard and Klaus B{\o}nnelykke",
year = "2020",
doi = "10.1038/s41467-020-19814-6",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses

AU - Ahluwalia, Tarunveer S.

AU - Eliasen, Anders U.

AU - Sevelsted, Astrid

AU - Pedersen, Casper-Emil T.

AU - Stokholm, Jakob

AU - Chawes, Bo

AU - Bork-Jensen, Jette

AU - Grarup, Niels

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Linneberg, Allan

AU - Sharma, Amitabh

AU - Weiss, Scott T.

AU - Evans, Michael D.

AU - Jackson, Daniel J.

AU - Morin, Andreanne

AU - Krogfelt, Karen A.

AU - Schjørring, Susanne

AU - Mortensen, Preben B.

AU - Hougaard, David M.

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Børglum, Anders D.

AU - Werge, Thomas

AU - Agerbo, Esben

AU - Gern, James E.

AU - Lemanske, Robert F.

AU - Ober, Carole

AU - Pedersen, Anders G.

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

PY - 2020

Y1 - 2020

N2 - Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises 2866 children experiencing severe asthma exacerbation between ages 2 and 6 years, and 65,415 non-asthmatic controls, and we replicate findings in 918 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohorts. We identify rs281379 near FUT2/MAMSTR on chromosome 19 as a novel risk locus (OR = 1.18 (95% CI = 1.11–1.25), Pdiscovery = 2.6 × 10−9) as well as a biologically plausible interaction between functional variants in FUT2 and ABO. We further discover and replicate a potential causal mechanism behind this interaction related to S. pneumoniae respiratory illnesses. These results suggest a novel mechanism of early childhood asthma and demonstrates the importance of phenotype-specificity for discovery of asthma genes and epistasis.

AB - Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises 2866 children experiencing severe asthma exacerbation between ages 2 and 6 years, and 65,415 non-asthmatic controls, and we replicate findings in 918 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohorts. We identify rs281379 near FUT2/MAMSTR on chromosome 19 as a novel risk locus (OR = 1.18 (95% CI = 1.11–1.25), Pdiscovery = 2.6 × 10−9) as well as a biologically plausible interaction between functional variants in FUT2 and ABO. We further discover and replicate a potential causal mechanism behind this interaction related to S. pneumoniae respiratory illnesses. These results suggest a novel mechanism of early childhood asthma and demonstrates the importance of phenotype-specificity for discovery of asthma genes and epistasis.

U2 - 10.1038/s41467-020-19814-6

DO - 10.1038/s41467-020-19814-6

M3 - Journal article

C2 - 33328473

AN - SCOPUS:85097613852

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 6398

ER -

ID: 255105029