Project description:The Environmental Determinants of Diabetes in the Young (TEDDY) Study investigates genetic and genetic-environmental interactions, including gestational events, childhood infections, dietary exposures, and other environmental factors after birth, in relation to the development of islet autoimmunity and type 1 diabetes (T1D). A consortium of six clinical centers assembled to participate in the development and implementation of the study to identify environmental triggers for the development of islet autoimmunity and T1D in genetically susceptible individuals. Beginning in 2004, the TEDDY study screened over 400,000 newborns for high-risk HLA-DR, DQ genotypes from both the general population and families already affected by T1D. The TEDDY study enrolled around 8,676 participants across six clinical centers worldwide (Finland, Germany, Sweden and three in the United States) in the 15-year prospective follow-up. Participants are followed every three months for islet autoantibody (IA) measurements with blood sampling until four years of age and then at least every six months until the age of 15. After the age of four, autoantibody positive participants continue to be followed at three month intervals and autoantibody negative participants are followed at six-month intervals. In addition to the analysis of autoantibodies, additional data and sample collection are performed at each visit. Parents collect monthly stool samples in early childhood. The parents also fill out questionnaires at regular intervals in connection with study visits and record information about diet and health status in the child's TEDDY Book between visits. Continued long-term follow-up of the currently active TEDDY participants will provide important scientific information on early childhood diet, reported and measured infections, vaccinations, and psychosocial stressors that may contribute to the development of type 1 diabetes and islet autoimmunity. Additional information on the TEDDY study is available in the following articles: The Environmental Determinants of Diabetes in the Young (TEDDY) Study. TEDDY Study Group. Annals of the New York Academy of Science, 2008 and TEDDY - The Environmental Determinants of Diabetes in the Young - An Observational Clinical Trial. Annals of the New York Academy of Science, 2006 <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=19120261">Annals of the New York Academy of Science, 2008</a> and TEDDY - The Environmental Determinants of Diabetes in the Young - An Observational Clinical Trial. <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=17130573">Annals of the New York Academy of Science, 2006</a> Details of the TEDDY protocol can be found in The Environmental Determinants of Diabetes in the Young (TEDDY): Genetic Criteria and International Diabetes Risk Screening of 421,000 infants. <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=21564455">Pediatric Diabetes, 2011</a> There are three substudies associated with the current TEDDY project release in dbGaP: <ul> <li>TEDDY SNP Array - <a href="study.cgi?study_id=phs001037">phs001037</a> with targeted SNP array data.</li> <li>TEDDY Microbiome - <a href="study.cgi?study_id=phs001443">phs001443</a> with metagenomic and 16S rRNA sequencing data.</li> <li>TEDDY Gene Expression - <a href="study.cgi?study_id=phs001562">phs001562</a> with gene expression data.</li> </ul>

Project description:Lipids were quantified in human plasma from the 1:3 matched TEDDY case-control subjects (Lee et al., 2013). Blood plasma was extracted following the methyl-tert-butyl ether (MTBE) extraction protocols. The choice of internal standards and chromatographic conditions was optimized by using toluene in the reconstitution solvent mixture to ensure that very lipophilic components like cholesteryl esters (CEs) and triacylglycerols (TAGs) are efficiently transferred to the ultrahigh-pressure liquid chromatography (UHPLC) column in the injection process. Lipids were analyzed by charged surface hybrid column electrospray ionization quadrupole time of flight tandem mass spectrometer (CSH-ESI QTOF MS/MS). The analytical ultra-high-pressure liquid chromatography (UHPLC) column is protected by a short guard column which was replaced after 400 injections while the UHPLC column was replaced after 1,200 serum (or plasma) extract injections. The sequence of column replacements were evaluated to ensure no detrimental effects were detected with respect to peak shapes, absolute or relative lipid retention times or reproducibility of quantifications. Automatic valve switching was used after each injection to reduce sample carryover for highly lipophilic compounds. This valve switching employed a dual solvent wash, first with a water/acetonitrile mixture (1:1, v/v) and subsequently with a 100% isopropanol wash. LC-BinBase was used as an untargeted approach for annotating chromatographic peaks and spectra against a dynamically built library of compounds. The quantified raw dataset was normalized by the SERRF bioinformatics pipeline [1]. In the LC-QTOF data, samples were removed before normalization if they failed the laboratory’s QC standards or were missing data for more than half of the compounds. The SERRF normalized data have been made available for identified compounds. Results data for unidentified compounds are available un-normalized. An explanation of the study design variables are explained in detail in a data dictionary provided in the raw data download section. References: 1) Lee HS, Burkhardt B, McLeod W, Smith S, Eberhard C, Lynch K, Hadley D, Rewers M, Simell O, She JX, Hagopian W, Lernmark A, Akolkar B, Ziegler AG, Krischer J, and the TEDDY Study Group: Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Diabetes/Metabolism Research and Reviews. Epub 2013 December 15. doi: 10.1002/dmrr.2510 (PubMed ID: 24339168). 2) Fan S, Kind T, Cajka T, Hazen SL, Tang WHW, Kaddurah-Daouk R, Irvin MR, Arnett DK, Barupal DK, Fiehn O: Systematic Error Removal Using Random Forest for Normalizing Large-Scale Untargeted Lipidomics Data. Anal Chem 2019, 91(5):3590-3596.

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TEDDY Gene Expression Study

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