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Protocol for a nested case-control study design for omics investigations in the Environmental Determinants of Islet Autoimmunity cohort.
Oakey, Helena; Giles, Lynne C; Thomson, Rebecca L; Lê Cao, Kim-Anh; Ashwood, Pat; Brown, James D; Knight, Emma J; Barry, Simon C; Craig, Maria E; Colman, Peter G; Davis, Elizabeth A; Hamilton-Williams, Emma E; Harrison, Leonard C; Haynes, Aveni; Kim, Ki Wook; Mallitt, Kylie-Ann; McGorm, Kelly; Morahan, Grant; Rawlinson, William D; Sinnott, Richard O; Soldatos, Georgia; Wentworth, John M; Couper, Jennifer J; Penno, Megan A S.
Afiliação
  • Oakey H; Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Giles LC; School of Public Health, The University of Adelaide, Adelaide, South Australia, Australia.
  • Thomson RL; Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Lê Cao KA; Melbourne Integrative Genomics, School of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia.
  • Ashwood P; Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Brown JD; Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Knight EJ; Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Barry SC; Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Craig ME; School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
  • Colman PG; Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
  • Davis EA; Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
  • Hamilton-Williams EE; Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
  • Harrison LC; Telethon Kids Institute Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
  • Haynes A; Faculty of Medicine, Frazer Institute, The University of Queensland Translational Research Institute, Brisbane, Queensland, Australia.
  • Kim KW; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • Mallitt KA; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
  • McGorm K; Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.
  • Morahan G; School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
  • Rawlinson WD; Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Sinnott RO; School of Clinical Medicine - Psychiatry and Mental Health, University of New South Wales, Sydney, New South Wales, Australia.
  • Soldatos G; Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Wentworth JM; Centre for Diabetes Research, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, Western Australia, Australia.
  • Couper JJ; Virology Research Laboratory, Serology and Virology Division, South Eastern Area Laboratory Services Microbiology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
  • Penno MAS; Melbourne eResearch Group, School of Computing and Information Services, University of Melbourne, Melbourne, Victoria, Australia.
Ann Med ; 55(1): 2198255, 2023 12.
Article em En | MEDLINE | ID: mdl-37043275
ABSTRACT

Background:

The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D.

Method:

A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case's onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood.

Conclusions:

This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation.KEY MESSAGESThe ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 2_ODS3 Base de dados: MEDLINE Assunto principal: Ilhotas Pancreáticas / Diabetes Mellitus Tipo 1 Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Child / Child, preschool / Female / Humans / Infant / Newborn / Pregnancy Idioma: En Revista: Ann Med Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 2_ODS3 Base de dados: MEDLINE Assunto principal: Ilhotas Pancreáticas / Diabetes Mellitus Tipo 1 Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Child / Child, preschool / Female / Humans / Infant / Newborn / Pregnancy Idioma: En Revista: Ann Med Ano de publicação: 2023 Tipo de documento: Article