A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways

Bustamante, Mariona, Standl, Marie, Bassat, Quique, Vilor-Tejedor, Natalia, Medina-Gomez, Carolina, Bonilla, Carolina, Ahluwalia, Tarunveer S., Bacelis, Jonas, Bradfield, Jonathan P., Tiesler, Carla M. T., Rivadeneira, Fernando, Ring, Susan, Vissing, Nadja H., Fink, Nadia R., Jugessur, Astanand, Mentch, Frank D., Ballester, Ferran, Kriebel, Jennifer, Kiefte-de Jong, Jessica C., Wolsk, Helene M., Llop, Sabrina, Thiering, Elisabeth, Beth, Systke A., Timpson, Nicholas J., Andersen, Josefine, Schulz, Holger, Jaddoe, Vincent W. V., Evans, David M., Waage, Johannes, Hakonarson, Hakon, Grant, Struan F. A., Jacobsson, Bo, Bonnelykke, Klaus, Bisgaard, Hans, Smith, George Davey, Moll, Henriette A., Heinrich, Joachim, Estivill, Xavier and Sunyer, Jordi (2016) A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways. Human Molecular Genetics, 25 18: 4127-4142. doi:10.1093/hmg/ddw264


Author Bustamante, Mariona
Standl, Marie
Bassat, Quique
Vilor-Tejedor, Natalia
Medina-Gomez, Carolina
Bonilla, Carolina
Ahluwalia, Tarunveer S.
Bacelis, Jonas
Bradfield, Jonathan P.
Tiesler, Carla M. T.
Rivadeneira, Fernando
Ring, Susan
Vissing, Nadja H.
Fink, Nadia R.
Jugessur, Astanand
Mentch, Frank D.
Ballester, Ferran
Kriebel, Jennifer
Kiefte-de Jong, Jessica C.
Wolsk, Helene M.
Llop, Sabrina
Thiering, Elisabeth
Beth, Systke A.
Timpson, Nicholas J.
Andersen, Josefine
Schulz, Holger
Jaddoe, Vincent W. V.
Evans, David M.
Waage, Johannes
Hakonarson, Hakon
Grant, Struan F. A.
Jacobsson, Bo
Bonnelykke, Klaus
Bisgaard, Hans
Smith, George Davey
Moll, Henriette A.
Heinrich, Joachim
Estivill, Xavier
Sunyer, Jordi
Title A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways
Formatted title
A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
0964-6906
Publication date 2016-09-15
Sub-type Article (original research)
DOI 10.1093/hmg/ddw264
Open Access Status Not yet assessed
Volume 25
Issue 18
Start page 4127
End page 4142
Total pages 16
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2017
Language eng
Formatted abstract
More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistical tests were applied to the 1000 Genomes imputed genotypic data. The meta-analysis (N=5758) followed by replication (N=3784) identified a genome-wide significant association between rs8111874 and diarrhoea at age 1 year. Conditional analysis suggested that the causal variant could be rs601338 (W154X) in the FUT2 gene. Children with the A allele, which results in a truncated FUT2 protein, had lower risk of diarrhoea. FUT2 participates in the production of histo-blood group antigens and has previously been implicated in the susceptibility to infections, including Rotavirus and Norovirus. Gene-set enrichment analysis suggested pathways related to the histo-blood group antigen production, and the regulation of ion transport and blood pressure. Among others, the gastrointestinal tract, and the immune and neuro-secretory systems were detected as relevant organs. In summary, this genome-wide association meta-analysis suggests the implication of the FUT2 gene in diarrhoeal disease in young children from the general population.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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