title: Widespread seasonal gene expression reveals annual differences in human immunity and physiology.
abstract: Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease.
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Xaquin Castro
authors.initials: XC
authors.lastname: Dopico
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Evangelou
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Ferreira
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Marcin L
authors.initials: ML
authors.lastname: Pekalski
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Smyth
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Nicholas
authors.identifier: http://orcid.org/0000-0003-0049-2204
authors.initials: N
authors.lastname: Cooper
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: Oliver S
authors.identifier: http://orcid.org/0000-0002-3388-5760
authors.initials: OS
authors.lastname: Burren
authors.affiliation: MRC International Nutrition Group at MRC Unit The Gambia &London School of Hygiene &Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Fulford
authors.affiliation: MRC International Nutrition Group at MRC Unit The Gambia &London School of Hygiene &Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Branwen J
authors.initials: BJ
authors.lastname: Hennig
authors.affiliation: MRC International Nutrition Group at MRC Unit The Gambia &London School of Hygiene &Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Ingolstaedter Landstr. 1, D 85764 Neuherberg, Germany.
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
authors.affiliation: CRTD-DFG Research Center for Regenerative Therapies Dresden, Paul Langerhans Institute Dresden, Medical Faculty, Technische Universität Dresden, Fetscherstrasse, 01307 Dresden, Germany.
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.|MRC Biostatistics Unit, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
authors.forename: Chris
authors.identifier: http://orcid.org/0000-0001-9755-1703
authors.initials: C
authors.lastname: Wallace
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000222:Adaptation, Physiological; D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005714:Gambia; D005786:Gene Expression Regulation / Q000502:physiology*; D005802:Genes, MHC Class II / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D044349:Oceania; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012621:Seasons; D059467:Transcriptome; D055815:Young Adult
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D012333:RNA, Messenger