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Bustamante, M.* ; Standl, M. ; Bassat, Q.* ; Vilor-Tejedor, N.* ; Medina-Gomez, C.* ; Bonilla, C.* ; Ahluwalia, T.S.* ; Bacelis, J.* ; Bradfield, J.P.* ; Tiesler, C.M. ; Rivadeneira, F.* ; Ring, S.* ; Vissing, N.H.* ; Fink, N.R.* ; Jugessur, A.* ; Mentch, F.D.* ; Ballester, F.* ; Kriebel, J. ; Kiefte-de Jong, J.C.* ; Wolsk, H.M.* ; Llop, S.* ; Thiering, E. ; Beth, S.A.* ; Timpson, N.J.* ; Andersen, J.* ; Schulz, H. ; Jaddoe, V.W.* ; Evans, D.M* ; Waage, J.* ; Hakonarson, H.* ; Grant, S.F.* ; Jacobsson, B.* ; Bønnelykke, K.* ; Bisgaard, H.* ; Smith, G.D.* ; Moll, H.A.* ; Heinrich, J. ; Estivill, X.* ; Sunyer, J.*

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

Hum. Mol. Genet. 25, 4127-4142 (2016)
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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 one year of age and around two 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=5,758) followed by replication (N=3,784) identified a genome-wide significant association between rs8111874 and diarrhoea at age one 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, 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Blood-group Antigens; Major Genetic-determinants; Non-secretor Status; Rotavirus Infection; Cytokine Responses; Vaccine Recipients; Nonsense Mutation; Crohn Disease; Susceptibility; Polymorphisms
Language
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 25, Issue: 18, Pages: 4127-4142 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-503900-001
G-503900-003
G-504091-002
DOI 10.1093/hmg/ddw264
WOS ID WOS:000395806000019
Scopus ID 85014387631
PubMed ID 27559109
Erfassungsdatum 2016-09-01
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