Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes

被引：0

作者：

Ingrid Brænne

Suna Onengut-Gumuscu

Ruoxi Chen

Ani W. Manichaikul

Stephen S. Rich

Wei-Min Chen

Charles R. Farber

机构：

[1] University of Virginia,Center for Public Health Genomics

[2] University of Virginia,Department of Public Health Sciences

[3] University of Virginia,Department of Biochemistry and Molecular Genetics

[4] University of Colorado,Anschutz Medical Campus, Barbara Davis Center for Childhood Diabetes

[5] University of Turku,Turku University Hospital

[6] Hospital District of Southwest Finland,Center for Biotechnology and Genomic Medicine

[7] Tampere University,Forschergruppe Diabetes E.V. and Institute of Diabetes Research, Helmholtz Zentrum München, Forschergruppe Diabetes, and Klinikum Rechts Der Isar

[8] Tampere University Hospital,Center for Regenerative Therapies

[9] National Institute for Health and Welfare,Department of Nutritional Epidemiology

[10] University of Oulu,Dr. Von Hauner Children’s Hospital, Department of Gastroenterology

[11] Oulu University Hospital,Bristol Medical School

[12] University of Kuopio,Center for Genetics

[13] Augusta University,undefined

[14] University of Florida,undefined

[15] Pediatric Endocrine Associates,undefined

[16] Technische Universität München,undefined

[17] TU Dresden,undefined

[18] University of Bonn,undefined

[19] Ludwig Maximillians University Munich,undefined

[20] Lund University,undefined

[21] Pacific Northwest Research Institute,undefined

[22] Children’s Hospital of Pittsburgh of UPMC,undefined

[23] University of South Florida,undefined

[24] University of Bristol,undefined

[25] Children’s Hospital Oakland Research Institute,undefined

[26] NIDDK Biosample Repository at Fisher BioServices,undefined

[27] Jinfiniti Biotech,undefined

[28] LLC,undefined

[29] National Institutes of Diabetes and Digestive and Kidney Diseases,undefined

[30] National Institutes of Allergy and Infectious Diseases,undefined

[31] Columbia University,undefined

[32] Florida State University,undefined

来源：

Scientific Reports | / 11卷

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摘要：

Significant progress has been made in elucidating genetic risk factors influencing Type 1 diabetes (T1D); however, features other than genetic variants that initiate and/or accelerate islet autoimmunity that lead to the development of clinical T1D remain largely unknown. We hypothesized that genetic and environmental risk factors can both contribute to T1D through dynamic alterations of molecular interactions in physiologic networks. To test this hypothesis, we utilized longitudinal blood transcriptomic profiles in The Environmental Determinants of Diabetes in the Young (TEDDY) study to generate gene co-expression networks. In network modules that contain immune response genes associated with T1D, we observed highly dynamic differences in module connectivity in the 600 days (~ 2 years) preceding clinical diagnosis of T1D. Our results suggest that gene co-expression is highly plastic and that connectivity differences in T1D-associated immune system genes influence the timing and development of clinical disease.

引用

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