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

Authors :
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.
Source :
Nature Communications; 12/16/2020, Vol. 11 Issue 1, p1-12, 12p
Publication Year :
2020

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), P<subscript>discovery</subscript> = 2.6 × 10<superscript>−9</superscript>) 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. Genetic variants discovered through genome-wide association studies for asthma together account for a small portion of the heritability. Here, the authors identify a possible epistatic relationship between coding variants in FUT2 and ABO, especially pronounced in severe and early onset asthma. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
11
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
147645847
Full Text :
https://doi.org/10.1038/s41467-020-19814-6