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

TEDDY Study Group; Ingrid Brænne; Suna Onengut-Gumuscu; Ruoxi Chen; Ani W Manichaikul; Stephen S Rich; Wei-Min Chen; Charles R Farber; Suvi Ahonen; Sami Oikarinen; Maria Lönnrot; Mirva Koreasalo; Kalle Kurppa; Leena Hakola; Anne Riikonen; Mari Åkerlund; Markus Mattila; Heikki Hyöty; Suvi Virtanen; Katri Lindfors

doi:10.1038/s41598-021-01840-z

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

TEDDY Study Group, Ingrid Brænne, Suna Onengut-Gumuscu, Ruoxi Chen, Ani W Manichaikul, Stephen S Rich, Wei-Min Chen, Charles R Farber, Suvi Ahonen, Sami Oikarinen, Maria Lönnrot, Mirva Koreasalo, Kalle Kurppa, Leena Hakola, Anne Riikonen, Mari Åkerlund, Markus Mattila, Heikki Hyöty, Suvi Virtanen, Katri Lindfors

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Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

5 Sitaatiot (Scopus)

Abstrakti

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.

Alkuperäiskieli	Englanti
Artikkeli	22651
Julkaisu	Scientific Reports
Vuosikerta	11
Numero	1
DOI - pysyväislinkit	https://doi.org/10.1038/s41598-021-01840-z
Tila	Julkaistu - 22 marrask. 2021
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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10.1038/s41598-021-01840-zLisenssi: CC BY

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TEDDY Study Group, Brænne, I., Onengut-Gumuscu, S., Chen, R., Manichaikul, A. W., Rich, S. S., Chen, W.-M., Farber, C. R., Ahonen, S., Oikarinen, S., Lönnrot, M., Koreasalo, M., Kurppa, K., Hakola, L., Riikonen, A., Åkerlund, M., Mattila, M., Hyöty, H., Virtanen, S., & Lindfors, K. (2021). Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes. Scientific Reports, 11(1), Artikkeli 22651. https://doi.org/10.1038/s41598-021-01840-z

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title = "Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes",

abstract = "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.",

keywords = "Case-Control Studies, Child, Child, Preschool, Computational Biology, Diabetes Mellitus, Type 1/genetics, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Male, Models, Statistical, Prospective Studies, Systems Biology, Transcriptome",

author = "{TEDDY Study Group} and Ingrid Br{\ae}nne and Suna Onengut-Gumuscu and Ruoxi Chen and Manichaikul, {Ani W} and Rich, {Stephen S} and Wei-Min Chen and Farber, {Charles R} and Suvi Ahonen and Sami Oikarinen and Maria L{\"o}nnrot and Mirva Koreasalo and Kalle Kurppa and Leena Hakola and Anne Riikonen and Mari {\AA}kerlund and Markus Mattila and Heikki Hy{\"o}ty and Suvi Virtanen and Katri Lindfors",

note = "{\textcopyright} 2021. The Author(s).",

year = "2021",

month = nov,

day = "22",

doi = "10.1038/s41598-021-01840-z",

language = "English",

volume = "11",

journal = "Scientific Reports",

issn = "2045-2322",

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TEDDY Study Group, Brænne, I, Onengut-Gumuscu, S, Chen, R, Manichaikul, AW, Rich, SS, Chen, W-M, Farber, CR, Ahonen, S , Oikarinen, S , Lönnrot, M , Koreasalo, M , Kurppa, K , Hakola, L, Riikonen, A, Åkerlund, M , Mattila, M , Hyöty, H , Virtanen, S & Lindfors, K 2021, 'Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes', Scientific Reports, Vuosikerta 11, Nro 1, 22651. https://doi.org/10.1038/s41598-021-01840-z

TY - JOUR

T1 - Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes

AU - TEDDY Study Group

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 - Ahonen, Suvi

AU - Oikarinen, Sami

AU - Lönnrot, Maria

AU - Koreasalo, Mirva

AU - Kurppa, Kalle

AU - Hakola, Leena

AU - Riikonen, Anne

AU - Åkerlund, Mari

AU - Mattila, Markus

AU - Hyöty, Heikki

AU - Virtanen, Suvi

AU - Lindfors, Katri

PY - 2021/11/22

Y1 - 2021/11/22

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.

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Computational Biology

KW - Diabetes Mellitus, Type 1/genetics

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Models, Statistical

KW - Prospective Studies

KW - Systems Biology

KW - Transcriptome

U2 - 10.1038/s41598-021-01840-z

DO - 10.1038/s41598-021-01840-z

M3 - Article

C2 - 34811390

SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 22651

ER -

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

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