TY - JOUR
T1 - Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
AU - Brænne, Ingrid
AU - Onengut-Gumuscu, Suna
AU - Chen, Ruoxi
AU - Manichaikul, Ani
AU - Rich, Stephen
AU - Chen, Wei-Min
AU - Farber, Charles
AU - TEDDY Study Group
A2 - Lernmark, Åke
A2 - Agardh, Daniel
A2 - Aronsson, Carin Andrén
A2 - Ask, Maria
A2 - Bennet, Rasmus
A2 - Cilio, Corrado
A2 - Engqvist, Helene
A2 - Ericson-Hallström, Emelie
A2 - Fransson, Lina
A2 - Gard, Thomas
A2 - Hansen, Monika
A2 - Jisser, Hanna
A2 - Johansen, Fredrik
A2 - Jonsdottir, Berglind
A2 - Jovic, Silvija
A2 - Larsson, Helena Elding
A2 - Lindström, Marielle
A2 - Lundgren, Markus
A2 - Maziarz, Marlena
A2 - Månsson-Martinez, Maria
A2 - Markan, Maria
A2 - Mestan, Zeliha
A2 - Ottosson, Karin
A2 - Rahmati, Kobra
A2 - Ramelius, Anita
A2 - Salami, Falastin
A2 - Sjöberg, Anette
A2 - Sjöberg, Birgitta
A2 - Svensson, Malin
A2 - Törn, Carina
A2 - Wallin, Anne
A2 - Wimar, Åsa
A2 - Åberg, Sofie
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-021-01840-z
DO - 10.1038/s41598-021-01840-z
M3 - Article
C2 - 34811390
AN - SCOPUS:85122116230
SN - 2045-2322
VL - 11
SP - 1
EP - 13
JO - Scientific Reports
JF - Scientific Reports
M1 - 22651
ER -