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

Ingrid Brænne, Suna Onengut-Gumuscu, Ruoxi Chen, Ani Manichaikul, Stephen Rich, Wei-Min Chen, Charles Farber, TEDDY Study Group, Åke Lernmark (Contributor), Daniel Agardh (Contributor), Carin Andrén Aronsson (Contributor), Maria Ask (Contributor), Rasmus Bennet (Contributor), Corrado Cilio (Contributor), Helene Engqvist (Contributor), Emelie Ericson-Hallström (Contributor), Lina Fransson (Contributor), Thomas Gard (Contributor), Monika Hansen (Contributor), Hanna Jisser (Contributor)Fredrik Johansen (Contributor), Berglind Jonsdottir (Contributor), Silvija Jovic (Contributor), Helena Elding Larsson (Contributor), Marielle Lindström (Contributor), Markus Lundgren (Contributor), Marlena Maziarz (Contributor), Maria Månsson-Martinez (Contributor), Maria Markan (Contributor), Zeliha Mestan (Contributor), Karin Ottosson (Contributor), Kobra Rahmati (Contributor), Anita Ramelius (Contributor), Falastin Salami (Contributor), Anette Sjöberg (Contributor), Birgitta Sjöberg (Contributor), Malin Svensson (Contributor), Carina Törn (Contributor), Anne Wallin (Contributor), Åsa Wimar (Contributor), Sofie Åberg (Contributor)

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number22651
Pages (from-to)1-13
JournalScientific Reports
Volume11
DOIs
Publication statusPublished - 2021 Dec

Subject classification (UKÄ)

  • Endocrinology and Diabetes

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