Epigenetics and diabetes
Prof Charlotte Ling
Dr Tina Rönn
Dr Emma Nilsson
Dr Karl Bacos
Dr Sonia Garcia-Calzon
Dr Alexander Perfilyev
Dr Sabrina Ruhrmann
PhD Student Cajsa Davegårdh
José Maria Costa Junior
Previous group member
Dr Marloes Dekker Nitert
Dr Siri Malmgren
Dr Louise Nilsson
Dr Sofia Salö
Dr Annika Lundstig
Dr Anders Olsson
Dr Tasnim Dayeh
Dr Madhu Bysani
Dr Petr Volkov
Dr Elin Hall
Type 2 diabetes is a polygenic disease characterized by hyperglycaemia due to impaired pancreatic beta-cell function and insulin resistance in peripheral target tissues such as skeletal muscle, adipose tissue and the liver. The disease develops as a conspiracy between the genetic background and the environment. Recent genome-wide association studies have identified more than 60 genetic variants associated with type 2 diabetes. Moreover, ageing, physical inactivity and obesity represent non-genetic risk factors for type 2 diabetes. The interaction between genes and environment may involve epigenetic factors, such as DNA methylation and histone modifications, to promote type 2 diabetes. Indeed, recent studies from our group and others propose that epigenetic factors play an important role in the growing incidence of type 2 diabetes. We were the first to demonstrate that DNA methylation plays a role in gene regulation in pancreatic islets from patients with type 2 diabetes. Additionally, we have performed genome-wide analyses of DNA methylation in pancreatic islets, skeletal muscle, adipose tissue and the liver from subjects with type 2 diabetes and non-diabetic controls. In these studies, we identified epigenetic alterations that are likely to contribute to the development of diabetes. We have also shown that age, diet, physical activity, birth weight and genetic variation influence the DNA methylation pattern in human pancreatic islets, skeletal muscle, adipose tissue and the liver. Nevertheless, our knowledge about the epigenetic mechanisms linking environmental factors and type 2 diabetes remains limited.
The overall objective of our research is to identify the key epigenetic mechanisms influencing the pathogenesis of T2D.
We are currently analysing DNA methylation and histone modifications in a number of human cohorts. Here, we examine if non-genetic and genetic factors as well as type 2 diabetes affect epigenetic variation in human tissues (Figure 1). We are further relating DNA methylation to gene expression, in vivo metabolism and type 2 diabetes. Furthermore, we are dissecting the role of epigenetic enzymes in development of type 2 diabetes.
Selected recent publications
1. Karl Bacos, Linn Gillberg, Petr Volkov, Anders H. Olsson, Torben Hansen, Oluf Pedersen, Anette Prior Gjesing, Hans Eiberg, Tiinamaija Tuomi, Peter Almgren, Leif Groop, Lena Eliasson, Allan Vaag, Tasnim Dayeh and Charlotte Ling
Blood-based biomarkers reflect age-associated epigenetic changes in human pancreatic islets and associate with insulin secretion and diabetes.
Nature Communications, 2016 Mar 31
2. Linn Gillberg, Alexander Perfilyev, Charlotte Brøns, Martin Thomasen, Louise G. Grunnet, Petr Volkov, Fredrik Rosqvist, David Iggman, Ingrid Dahlman, Ulf Risérus, Tina Rönn, Emma Nilsson, Allan Vaag and Charlotte Ling
Adipose tissue transcriptomics and epigenomics in low birth weight men and controls – role of high-fat overfeeding.
Diabetologia, 2016 Jan 11
3. Emma Nilsson, Ashok Matte, Alexander Perfilyev, Vanessa D. de Mello, Pirjo Käkelä, Jussi Pihlajamäki and Charlotte Ling
Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels.
Journal of Clinical Endocrinology and Metabolism 2015 Nov;100(11):E1491-501
4. Tina Rönn, Petr Volkov, Linn Gillberg, Milana Kokosar, Alexander Perfilyev, Anna Louisa Jacobsen, Sine W. Jørgensen, Charlotte Brøns, Per Anders Jansson, Karl-Fredrik Eriksson, Oluf Pedersen, Torben Hansen, Leif Groop, Elisabet Stener-Victorin, Allan Vaag, Emma Nilsson and Charlotte Ling
Age, BMI and HbA1c levels are associated with altered DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.
Human Molecular Genetics 2015 Jul 1;24(13):3792-813.
5. Elin Hall, Petr Volkov, Tasnim Dayeh, Jonathan Lou S. Esguerra, Sofia Salö, Lena Eliasson, Tina Rönn, Karl Bacos and Charlotte Ling
Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets
Genome Biology, 2014 Dec 3;15(12):522.
6. Anders H Olsson, Petr Volkov, Karl Bacos, Tasnim Dayeh, Elin Hall, Emma A Nilsson, Claes Ladenvall, Tina Rönn and Charlotte Ling
Genome-Wide Associations between Genetic and Epigenetic Variation Influence mRNA Expression and Insulin Secretion in Human Pancreatic Islets.
PLoS Genetics, 2014 Nov 6;10(11):e1004735.
7. Emma Nilsson, Per Anders Jansson, Alexander Perfilyev, Petr Volkov, Maria Pedersen, Maria K Svensson, Pernille Poulsen, Joao Fadista, Tina Rönn, Bente Klarlund-Pedersen, Camilla Scheele, Allan Vaag and Charlotte Ling
Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from monozygotic twin pairs discordant for type 2 diabetes.
Diabetes, 2014, Sep;63(9):2962-76.
8. Tasnim Dayeh, Petr Volkov, Sofia Salö, Elin Hall, Emma Nilsson, Anders H. Olsson, Clare L. Kirkpatrick, Claes Wollheim, Lena Eliasson, Tina Rönn, Karl Bacos and Charlotte Ling
Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion
PLoS Genetics, 2014 Mar 6;10(3):e1004160.
9. Tina Rönn, Petr Volkov, Cajsa Davegård, Tasnim Dayeh, Elin Hall, Targ Elgzyri, Åsa Tornberg, Marloes Dekker-Nitert, Karl-Fredrik Eriksson, Helena Jones, Leif Groop and Charlotte Ling
A six months exercise intervention influences the epigenetic pattern in human adipose tissue
PLoS Genetics 2013 Jun;9(6):e1003572.
10. Tasnim A. Dayeh, Anders H. Olsson, Peter Volkov, Peter Almgren, Tina Rönn and Charlotte Ling
Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.
Diabetologia 2013 May;56(5):1036-46.
11. Marloes Dekker Nitert, Tasnim Dayeh, Peter Volkov, Targ Elgzyri, Elin Hall, Emma Nilsson, Beatrice T. Yang, Stefan Lang, Hemang Parikh, Ylva Wessman, Holger Weishaupt, Joanne Attema, Mia Ländin, Nils Wierup, Peter Almgren, Per-Anders Jansson, Tina Rönn, Ola Hansson, Karl-Fredrik Eriksson, Leif Groop and Charlotte Ling
Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle from First Degree Relatives of Patients with Type 2 Diabetes
Diabetes 2012 Dec;61(12):3322-32
12. Thomas Koeck, Anders H Olsson, Marloes Dekker Nitert, Vladimir V. Sharoyko, Claes Ladenvall, Olga Kotova, Erwin Reiling, Tina Rönn, Hemang Parikh, Jalal Taneera, Johan G Eriksson, Metodi D Metodiev, Nils-Göran Larsson, Alexander Balhuizen, Holger Luthman, Alena Stančáková, Johanna Kuusisto, Markku Laakso, Pernille Poulsen, Allan Vaag, Leif Groop, Valeriya Lyssenko, Hindrik Mulder and Charlotte Ling
A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.
Cell Metabolism 2011 Jan 5;13(1):80-91.