title: Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study.
abstract: OBJECTIVE
  The Environmental Determinants of Diabetes in the Young planned biomarker discovery studies on longitudinal samples for persistent confirmed islet cell autoantibodies and type 1 diabetes using dietary biomarkers, metabolomics, microbiome/viral metagenomics and gene expression.
  
  
  METHODS
  This article describes the details of planning The Environmental Determinants of Diabetes in the Young biomarker discovery studies using a nested case-control design that was chosen as an alternative to the full cohort analysis. In the frame of a nested case-control design, it guides the choice of matching factors, selection of controls, preparation of external quality control samples and reduction of batch effects along with proper sample allocation.
  
  
  CONCLUSIONS
  Our design is to reduce potential bias and retain study power while reducing the costs by limiting the numbers of samples requiring laboratory analyses. It also covers two primary end points (the occurrence of diabetes-related autoantibodies and the diagnosis of type 1 diabetes). The resulting list of case-control matched samples for each laboratory was augmented with external quality control samples.
authors: Hye-Seung
authors: HS
authors: Lee
authors: Brant R
authors: BR
authors: Burkhardt
authors: Wendy
authors: W
authors: McLeod
authors: Susan
authors: S
authors: Smith
authors: Chris
authors: C
authors: Eberhard
authors: Kristian
authors: K
authors: Lynch
authors: David
authors: D
authors: Hadley
authors: Marian
authors: M
authors: Rewers
authors: Olli
authors: O
authors: Simell
authors: Jin-Xiong
authors: JX
authors: She
authors: Bill
authors: B
authors: Hagopian
authors: Ake
authors: A
authors: Lernmark
authors: Beena
authors: B
authors: Akolkar
authors: Anette G
authors: AG
authors: Ziegler
authors: Jeffrey P
authors: JP
authors: Krischer
mesh_terms: D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004032:Diet; D004812:Epidemiologic Methods; D015870:Gene Expression; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D055432:Metabolomics; D056186:Metagenomics; D064307:Microbiota
chemical_list: D001323:Autoantibodies; D015415:Biomarkers
keywords: TEDDY; batch effects; biomarker discovery; nested case-control design; type 1 diabetes