A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways
Year: 2016
Type: review
Study design: Observational Study
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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddw264
Authors: Mariona Bustamante, Marie Standl, Quique Bassat, Natalia Vilor-Tejedor, Carolina Medina-Gomez, Carolina Bonilla, Tarunveer S. Ahluwalia, Jonas Bacelis, Jonathan P. Bradfield, Carla M.T. Tiesler, Fernando Rivadeneira, Susan Ring, Nadja H. Vissing, Nadia R. Fink, Astanand Jugessur, Frank D. Mentch, Ferran Ballester, Jennifer Kriebel, Jessica C. Kiefte-de Jong, Helene M. Wolsk, Sabrina Llop, Elisabeth Thiering, Systke A. Beth, Nicholas J. Timpson, Josefine Andersen, Holger Schulz, Vincent W.V. Jaddoe, David M. Evans, Johannes Waage, Hakon Hakonarson, Struan F.A. Grant, Bo Jacobsson, Klaus Bønnelykke, Hans Bisgaard, George Davey Smith, Henriette A. Moll, Joachim Heinrich, Xavier Estivill, Jordi Sunyer
Institutions: Universitat Pompeu Fabra, Center for Research in Environmental Epidemiology, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Helmholtz Munich, Manhiça Health Research Centre, Universitat de Barcelona, Erasmus MC, University of Bristol, MRC Integrative Epidemiology Unit, University of Copenhagen, Gentofte Hospital, Copenhagen Prospective Studies on Asthma in Childhood, University of Gothenburg, Children's Hospital of Philadelphia, Ludwig-Maximilians-Universität München, Norwegian Institute of Public Health, Universitat Jaume I, Universitat de València, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Leiden University, Erasmus MC - Sophia Children’s Hospital, Translational Research Institute, The University of Queensland, University of Pennsylvania, LMU Klinikum, Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, Sidra Medical and Research Center, Municipal Institute for Medical Research, Hospital del Mar Research Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Mead Johnson Nutrition, Strategiske Forskningsråd, Wellcome Trust, European Commission, University of Bristol, ZonMw, Erasmus Universiteit Rotterdam, Generalitat de Catalunya, Erasmus Medisch Centrum, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Ministerio de Economía y Competitividad, Generalitat Valenciana, Lundbeckfonden, Helmholtz-Zentrum für Umweltforschung, Danmarks Frie Forskningsfond, Norges Forskningsråd, Ministeriet Sundhed Forebyggelse, Svenska Läkaresällskapet, Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, National Institutes of Health, Medical Research Council, Instituto de Salud Carlos III, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1192034430, G1238845470, G1324243109, G1365915403, G149876332, G1516964218, G1769080647, G1885339171, G1948905973, G1987169411, G2169357564, G2276760851, G2340656413, G235045266, G2716889063, G3340096288, Genome Wide Association Study for Childhood Obesity, G352550759, Gene-Environment Interactions in an Autism Birth Cohort, G3805357244, G3831911591, G4072675998, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G4507075526, G5001017760, G5224277619, G5562631338, NORWAY MOTHER AND CHILD COHORT STUDY: CONTINUED SPECIMEN, G6002092336, G6119919417, G6383967859, G6423108142, G6520203987, G6563565772, G6689231961, G7572373960, G8041689659, G80777371, Expenses associated with Cornell Summer School Programme 2007
OpenAlex ID: W2509936128