Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity
Authors: Norris Jill M. , Lee Hye-Seung , Frederiksen Brittni , Erlund Iris , Uusitalo Ulla , Yang Jimin , Lernmark Åke , Simell Olli , Toppari Jorma , Rewers Marian , Ziegler Anette-G. , She Jin-Xiong , Onengut-Gumuscu Suna , Chen Wei-Min , Rich Stephen S. , Sundvall Jouko , Akolkar Beena , Krischer Jeffrey , Virtanen Suvi M. , Hagopian William ,   The TEDDY Study Group, Rewers Marian , Bautista Kimberly , Baxter Judith , Bedoy Ruth , Felipe-Morales Daniel , Driscoll Kimberly , Frohnert Brigitte I. , Gesualdo Patricia , Hoffman Michelle , Karban Rachel , Liu Edwin , Norris Jill , Samper-Imaz Adela , Steck Andrea , Waugh Kathleen , Wright Hali , Toppari Jorma , Simell Olli G. , Adamsson Annika , Ahonen Suvi , Hyöty Heikki , Ilonen Jorma , Jokipuu Sanna , Kallio Tiina , Karlsson Leena , Kähönen Miia , Knip Mikael , Kovanen Lea , Koreasalo Mirva , Kurppa Kalle , Latva-aho Tiina , Lönnrot Maria , Mäntymäki Elina , Multasuo Katja , Mykkänen Juha , Niininen Tiina , Niinistö Sari , Nyblom Mia , Rajala Petra , Rautanen Jenna , Riikonen Anne , Riikonen Mika , Rouhiainen Jenni , Romo Minna , Simell Tuula , Simell Ville , Sjöberg Maija , Stenius Aino , Leppänen Maria , Vainionpää Sini , Varjonen Eeva , Veijola Riitta , Virtanen Suvi M. , Vähä-Mäkilä Mari , Åkerlund Mari , Lindfors Katri , She Jin-Xiong , Schatz Desmond , Hopkins Diane , Steed Leigh , Thomas Jamie , Adams Janey , Silvis Katherine , Haller Michael , Gardiner Melissa , McIndoe Richard , Sharma Ashok , Williams Joshua , Young Gabriela , Anderson Stephen W. , Jacobsen Laura , Ziegler Anette G. , Beyerlein Andreas , Bonifacio Ezio , Hummel Michael , Hummel Sandra , Foterek Kristina , Janz Nicole , Kersting Mathilde , Knopff Annette , Koletzko Sibylle , Peplow Claudia , Roth Roswith , Scholz Marlon , Stock Joanna , Warncke Katharina , Wendel Lorena , Winkler Christiane , Lernmark Åke , Agardh Daniel , Aronsson Carin Andrén , Ask Maria , Bremer Jenny , Carlsson Ulla-Marie , Cilio Corrado , Ericson-Hallström Emelie , Fransson Lina , Gard Thomas , Gerardsson Joanna , Bennet Rasmus , Hansen Monica , Hansson Gertie , Hyberg Susanne , Johansen Fredrik , Jonsdottir Berglind , Larsson Helena Elding , Lindström Marielle , Lundgren Markus , Månsson-Martinez Maria , Markan Maria , Melin Jessica , Mestan Zeliha , Ottosson Karin , Rahmati Kobra , Ramelius Anita , Salami Falastin , Sibthorpe Sara , Sjöberg Birgitta , Swartling Ulrica , Amboh Evelyn Tekum , Törn Carina , Wallin Anne , Wimar Åsa , Åberg Sofie , Hagopian William A. , Killian Michael , Crouch Claire Cowen , Skidmore Jennifer , Carson Josephine , Dalzell Maria , Dunson Kayleen , Hervey Rachel , Johnson Corbin , Lyons Rachel , Meyer Arlene , Mulenga Denise , Tarr Alexander , Uland Morgan , Willis John , Becker Dorothy , Franciscus Margaret , Dalmagro-Elias Smith MaryEllen , Daftary Ashi , Klein Mary Beth , Yates Chrystal , Krischer Jeffrey P. , Abbondondolo Michael , Austin-Gonzalez Sarah , Avendano Maryouri , Baethke Sandra , Brown Rasheedah , Burkhardt Brant , Butterworth Martha , Clasen Joanna , Cuthbertson David , Eberhard Christopher , Fiske Steven , Garcia Dena , Garmeson Jennifer , Gowda Veena , Heyman Kathleen , Laras Francisco Perez , Lee Hye-Seung , Liu Shu , Liu Xiang , Lynch Kristian , Malloy Jamie , McCarthy Cristina , Meulemans Steven , Parikh Hemang , Shaffer Chris , Smith Laura , Smith Susan , Sulman Noah , Tamura Roy , Uusitalo Ulla , Vehik Kendra , Vijayakandipan Ponni , Wood Keith , Yang Jimin , Akolkar Beena , Bourcier Kasia , Briese Thomas , Johnson Suzanne Bennett , Triplett Eric , Yu Liping , Miao Dongmei , Bingley Polly , Williams Alistair , Chandler Kyla , Rokni Saba , Williams Claire , Wyatt Rebecca , George Gifty , Grace Sian , Erlund Iris , Salminen Irma , Sundvall Jouko , Leiviskä Jaana , Kangas Nina , Arohonka Petra , Erlich Henry , Mack Steven J. , Fear Anna Lisa , Ke Sandra , Mulholland Niveen , Rich Stephen S. , Chen Wei-Min , Onengut-Gumuscu Suna , Farber Emily , Pickin Rebecca Roche , Davis Jordan , Gallo Dan , Bonnie Jessica , Campolieto Paul 
Published: October 2017

We examined the association between plasma 25-hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested case-control study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentration was measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.