Signatures of TSPAN8 variants associated with human metabolic regulation and diseases
Tisham De,
Angela Goncalves,
Doug Speed,
Philippe Froguel,
Daniel J. Gaffney,
Michael R. Johnson,
Marjo-Riitta Jarvelin,
Lachlan JM. Coin
Affiliations
Tisham De
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Department of Genomics of Common Diseases, Imperial College London, London, UK; Department of Metabolism, Imperial College London, London, UK; Corresponding author
Angela Goncalves
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
Doug Speed
Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark; Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Aarhus, Denmark; Quantitative Genetics and Genomics (QGG), Aarhus University, Aarhus, Denmark
Philippe Froguel
Department of Genomics of Common Diseases, Imperial College London, London, UK; Department of Metabolism, Imperial College London, London, UK; Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Université de Lille, Institut Pasteur de Lille, Lille University Hospital, Lille, France
Daniel J. Gaffney
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
Michael R. Johnson
Department of Brain Sciences, Imperial College London, London, UK
Marjo-Riitta Jarvelin
Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Unit of Primary Health Care and Medical Research Center, Oulu University Hospital, Oulu, Finland; Department of Epidemiology and Biostatistics, Medical Research Council–Public Health England Centre for Environment and Health, Imperial College London, London, UK; Biocenter Oulu, University of Oulu, Oulu, Finland
Lachlan JM. Coin
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Department of Genomics of Common Diseases, Imperial College London, London, UK; Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Summary: Here, with the example of common copy number variation (CNV) in the TSPAN8 gene, we present an important piece of work in the field of CNV detection, that is, CNV association with complex human traits such as 1H NMR metabolomic phenotypes and an example of functional characterization of CNVs among human induced pluripotent stem cells (HipSci). We report TSPAN8 exon 11 (ENSE00003720745) as a pleiotropic locus associated with metabolomic regulation and show that its biology is associated with several metabolic diseases such as type 2 diabetes (T2D) and cancer. Our results further demonstrate the power of multivariate association models over univariate methods and define metabolomic signatures for variants in TSPAN8.
