FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses
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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.
I: Nature Communications, Bind 11, 6398, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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