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 tha...

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Autores principales:	Ingrid Brænne, Suna Onengut-Gumuscu, Ruoxi Chen, Ani W. Manichaikul, Stephen S. Rich, Wei-Min Chen, Charles R. Farber, the TEDDY Study Group
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9421c0710b934d629143b663772e71fc
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spelling	oai:doaj.org-article:9421c0710b934d629143b663772e71fc2021-11-28T12:20:55ZDynamic changes in immune gene co-expression networks predict development of type 1 diabetes10.1038/s41598-021-01840-z2045-2322https://doaj.org/article/9421c0710b934d629143b663772e71fc2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01840-zhttps://doaj.org/toc/2045-2322Abstract 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.Ingrid BrænneSuna Onengut-GumuscuRuoxi ChenAni W. ManichaikulStephen S. RichWei-Min ChenCharles R. Farberthe TEDDY Study GroupNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ingrid Brænne Suna Onengut-Gumuscu Ruoxi Chen Ani W. Manichaikul Stephen S. Rich Wei-Min Chen Charles R. Farber the TEDDY Study Group Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
description	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.
format	article
author	Ingrid Brænne Suna Onengut-Gumuscu Ruoxi Chen Ani W. Manichaikul Stephen S. Rich Wei-Min Chen Charles R. Farber the TEDDY Study Group
author_facet	Ingrid Brænne Suna Onengut-Gumuscu Ruoxi Chen Ani W. Manichaikul Stephen S. Rich Wei-Min Chen Charles R. Farber the TEDDY Study Group
author_sort	Ingrid Brænne
title	Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
title_short	Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
title_full	Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
title_fullStr	Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
title_full_unstemmed	Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
title_sort	dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9421c0710b934d629143b663772e71fc
work_keys_str_mv	AT ingridbrænne dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes AT sunaonengutgumuscu dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes AT ruoxichen dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes AT aniwmanichaikul dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes AT stephensrich dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes AT weiminchen dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes AT charlesrfarber dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes AT theteddystudygroup dynamicchangesinimmunegenecoexpressionnetworkspredictdevelopmentoftype1diabetes
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Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes

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