TY - JOUR
T1 - Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
AU - Repository
AU - RNA Laboratory and Gene Expression Laboratory
AU - SNP Laboratory
AU - The TEDDY study group
AU - Colorado Clinical Center
AU - Finland Clinical Center
AU - Georgia/Florida Clinical Center
AU - Germany Clinical Center
AU - Sweden Clinical Center
AU - Washington Clinical Center
AU - Pennsylvania Satellite Center
AU - Data Coordinating Center
AU - Autoantibody Reference Laboratories
AU - HLA Reference Laboratory
AU - Brænne, Ingrid
AU - Onengut-Gumuscu, Suna
AU - Chen, Ruoxi
AU - Manichaikul, Ani W.
AU - Rich, Stephen S.
AU - Chen, Wei Min
AU - Farber, Charles R.
AU - Rewers, Marian
AU - Barbour, Aaron
AU - Bautista, Kimberly
AU - Baxter, Judith
AU - Felipe-Morales, Daniel
AU - Driscoll, Kimberly
AU - Frohnert, Brigitte I.
AU - Stahl, Marisa
AU - Gesualdo, Patricia
AU - Hoffman, Michelle
AU - Karban, Rachel
AU - Liu, Edwin
AU - Norris, Jill
AU - Peacock, Stesha
AU - Shorrosh, Hanan
AU - Steck, Andrea
AU - Stern, Megan
AU - Villegas, Erica
AU - Waugh, Kathleen
AU - Toppari, Jorma
AU - Simell, Olli G.
AU - Adamsson, Annika
AU - Ahonen, Suvi
AU - Åkerlund, Mari
AU - Hakola, Leena
AU - Hekkala, Anne
AU - Holappa, Henna
AU - Hyöty, Heikki
AU - Ikonen, Anni
AU - Ilonen, Jorma
AU - Jäminki, Sinikka
AU - Jokipuu, Sanna
AU - Karlsson, Leena
AU - Kero, Jukka
AU - Kähönen, Miia
AU - Knip, Mikael
AU - Koivikko, Minna Liisa
AU - Koskinen, Merja
AU - Koreasalo, Mirva
AU - Kurppa, Kalle
AU - Kytölä, Jarita
AU - McIndoe, Richard
AU - Sharma, Ashok
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.
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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
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 22651
ER -
