PubMed ID:
25422107
Public Release Type:
Journal
Publication Year: 2015
Affiliation: Pediatric Epidemiology Center, Department of Pediatrics, University of South Florida, Tampa, FL.
DOI:
https://doi.org/10.2337/db14-1497
Authors:
Knip M,
Veijola R,
Ilonen J,
Ilonen J,
Toppari J,
Toppari J,
Liu X,
Liu S,
Aardal Eriksson E,
Abbondondolo M,
Aberg S,
Adamsson A,
Agardh D,
Akerlund M,
Akolkar B,
Akolkar B,
Anderson SW,
Andrén Aronsson C,
Ansong C,
Ask M,
Austin-Gonzalez S,
Ayres S,
Bautista K,
Baxter J,
Becker D,
Bedoy R,
Bennett Johnson S,
Beyerlein A,
Bingley P,
Boldison J,
Bonifacio E,
Bonnie J,
Bourcier K,
Bremer J,
Briese T,
Brown R,
Burkhardt B,
Butterly J,
Butterworth M,
Campolieto P,
Carlsson UM,
Carreno G,
Caygill C,
Chandler K,
Chen WM,
Chen WM,
Cilio C,
Cowen Crouch C,
Cuthbertson D,
Daftary A,
Dalmagro-Elias Smith ME,
Davis J,
Defelice B,
Dunson K,
Eberhard C,
Ekstrand C,
Elding Larsson H,
Ericson-Hallström E,
Erlich H,
Erlich H,
Erlund I,
Farber E,
Fear AL,
Felipe-Morales D,
Fiehn O,
Fiske S,
Foghis G,
Foterek K,
Franciscus M,
Fransson L,
Frohnert B,
Gallo D,
Garcia D,
Gardiner M,
Gard T,
Gaur VP,
Geoghan I,
Gerardsson J,
Gesualdo P,
Gowda V,
Grapov D,
Hadley D,
Hadley D,
Hagopian W,
Hagopian WA,
Håkansson R,
Haller M,
Hansen M,
Hansson G,
Heaney D,
Hervey R,
Higgins H,
Hoffman M,
Hopkins D,
Hummel M,
Hummel S,
Hyberg S,
Hyöty H,
Jiang N,
Johansen F,
Johnson C,
Jonasdottir B,
Jonsson L,
Kähönen M,
Karban R,
Kersting M,
Ke S,
Killian M,
Kind T,
Klein MB,
Knopff A,
Koivu A,
Koletzko S,
Koreasalo M,
Krischer J,
Krischer JP,
Kurppa K,
Lee HS,
Lee HS,
Lehtonen M,
Leiviskä J,
Lernmark A,
Lernmark Å,
Lernmark B,
Little RR,
Liu E,
Liu H,
Liu H,
Long A,
Lönn Karlsson E,
Lönnrot M,
Lundgren IM,
Lynch K,
Lyons R,
Mack SJ,
Mack SJ,
Malloy J,
Månsson-Martinez M,
Mäntymäki E,
Marcovina SM,
Markan M,
Massadakis T,
McCarthy C,
McIndoe R,
McIndoe R,
McLeod W,
Melin J,
Mestan Z,
Metz TO,
Meyer A,
Miao D,
Mitchell HD,
Mulenga D,
Multasuo K,
Mykkänen J,
Mykkänen J,
Nechtman J,
Nechtman J,
Nezirevic Dernroth D,
Niininen T,
Norris J,
Nyblom M,
Oberste S,
Onengut-Gumuscu S,
Onengut-Gumuscu S,
Palazoglu M,
Payne M,
Pearson J,
Peplow C,
Petrosino J,
Rahmati K,
Rajala P,
Ramelius A,
Rautanen J,
Rewers M,
Rewers M,
Rich SS,
Rich SS,
Ridewood S,
Riikonen A,
Roche Pickin R,
Rokni S,
Romo M,
Roth R,
Salami F,
Salminen I,
Samper-Imaz A,
Schatz D,
Schatz D,
Schulte E,
Scott E,
Sedig Järvirova M,
Shaffer C,
Shankar M,
Sharma A,
Sheehan E,
She JX,
She JX,
She JX,
Sibthorpe S,
Silvis K,
Simell O,
Simell OG,
Simell S,
Simell T,
Simell V,
Sjöberg B,
Sjöberg M,
Skidmore J,
Smith L,
Smith RD,
Smith S,
Stabbert J,
Steck A,
Steck AK,
Steed L,
Stenius A,
Stock J,
Strauss E,
Sundvall J,
Swartling U,
Tamura R,
TEDDY Study Group,
Tennill AL,
Thomas J,
Törn C,
Törn C,
Triplett E,
Trulsson E,
Uusitalo U,
Valdiviez L,
Varjonen E,
Vehik K,
Vijayakandipan P,
Virtanen SM,
Wallin A,
Wancewicz B,
Warncke K,
Waugh K,
Webb-Robertson BJ,
Wikoff B,
Williams A,
Williams J,
Willis J,
Wimar A,
Winkler C,
Wohlgemuth G,
Wong J,
Wood K,
Wright H,
Wyatt R,
Yang J,
Yan X,
Yates C,
Yu L,
Zhao Y,
Ziegler A,
Ziegler AG
Studies:
The Environmental Determinants of Diabetes in the Young
The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,677 children enrolled from birth who carry HLA-susceptibility genotypes for development of islet autoantibodies (IA) and type 1 diabetes (T1D). During the median follow-up time of 57 months, 350 children developed at least one persistent IA (GAD antibody, IA-2A, or micro insulin autoantibodies) and 84 of them progressed to T1D. We genotyped 5,164 Caucasian children for 41 non-HLA single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with T1D in the genome-wide association scan meta-analysis conducted by the Type 1 Diabetes Genetics Consortium. In TEDDY participants carrying high-risk HLA genotypes, eight SNPs achieved significant association to development of IA using time-to-event analysis (P < 0.05), whereof four were significant after adjustment for multiple testing (P < 0.0012): rs2476601 in PTPN22 (hazard ratio [HR] 1.54 [95% CI 1.27-1.88]), rs2292239 in ERBB3 (HR 1.33 [95% CI 1.14-1.55]), rs3184504 in SH2B3 (HR 1.38 [95% CI 1.19-1.61]), and rs1004446 in INS (HR 0.77 [0.66-0.90]). These SNPs were also significantly associated with T1D in particular: rs2476601 (HR 2.42 [95% CI 1.70-3.44]). Although genes in the HLA region remain the most important genetic risk factors for T1D, other non-HLA genetic factors contribute to IA, a first step in the pathogenesis of T1D, and the progression of the disease.