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5 results on '"Ewan R Pearson"'

1. Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Author

Andreas L. Birkenfeld, Mickaël Canouil, Yan Borné, Emma Ahlqvist, Marju Orho-Melander, Olle Melander, Dina Mansour Aly, Ewan R. Pearson, Erik Renström, Maykel López Rodríguez, Angela C. Shore, Cheng Luan, Rui Gao, Andreas Peter, Robert Wagner, Leif Groop, Yang De Marinis, Mun-Gwan Hong, Hans-Ulrich Häring, Jan Nilsson, Norbert Stefan, Markku Laakso, Paul W. Franks, Morris F. White, Peter M. Nilsson, Jianping Weng, Kevin L. Duffin, Ajit Regmi, Jonathan M. Wilson, William C. Roell, Gunnar Engström, Jochen M. Schwenk, Allan Vaag, Minna U. Kaikkonen, Jürgen Machann, Andrea Natali, Claes B. Wollheim, Rongya Tao, Chuanyan Wu, Andreas Fritsche, Harald Staiger, Faisel Khan, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Leif Groop Research Group, and Clinicum

Subjects
Follistatin, endocrine system diseases, General Physics and Astronomy, Adipose tissue, Type 2 diabetes, Genome-wide association studies, MYOSTATIN, GLUCOSE, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, P446L VARIANT, Insulin, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, biology, Glucokinase regulatory protein, Fatty liver, Middle Aged, 3. Good health, BINDING-PROTEIN, Adipose Tissue, embryonic structures, TRIGLYCERIDE, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, endocrine system, Science, 030209 endocrinology & metabolism, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Humans, Secretion, 030304 developmental biology, Adaptor Proteins, Signal Transducing, business.industry, Fatty acid, nutritional and metabolic diseases, General Chemistry, medicine.disease, GENE, MICE, Endocrinology, ACTIVIN-A, chemistry, Diabetes Mellitus, Type 2, 3121 General medicine, internal medicine and other clinical medicine, biology.protein, Hepatocytes, Insulin Resistance, business, Genome-Wide Association Study, GLUCOKINASE
Abstract

The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p, Follistatin promotes in type 2 diabetes (T2D) pathogenesis in model animals and is elevated in patients with T2D. Here the authors report that plasma follistatin associates with increased risk of incident T2D in two longitudinal cohorts, and show that follistatin regulates insulin-induced suppression lipolysis in cultured human adipocytes.

Published
2021
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2. Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

Author

Andrew A. Brown, Juan J. Fernandez-Tajes, Mun-gwan Hong, Caroline A. Brorsson, Robert W. Koivula, David Davtian, Théo Dupuis, Ambra Sartori, Theodora-Dafni Michalettou, Ian M. Forgie, Jonathan Adam, Kristine H. Allin, Robert Caiazzo, Henna Cederberg, Federico De Masi, Petra J. M. Elders, Giuseppe N. Giordano, Mark Haid, Torben Hansen, Tue H. Hansen, Andrew T. Hattersley, Alison J. Heggie, Cédric Howald, Angus G. Jones, Tarja Kokkola, Markku Laakso, Anubha Mahajan, Andrea Mari, Timothy J. McDonald, Donna McEvoy, Miranda Mourby, Petra B. Musholt, Birgitte Nilsson, Francois Pattou, Deborah Penet, Violeta Raverdy, Martin Ridderstråle, Luciana Romano, Femke Rutters, Sapna Sharma, Harriet Teare, Leen ‘t Hart, Konstantinos D. Tsirigos, Jagadish Vangipurapu, Henrik Vestergaard, Søren Brunak, Paul W. Franks, Gary Frost, Harald Grallert, Bernd Jablonka, Mark I. McCarthy, Imre Pavo, Oluf Pedersen, Hartmut Ruetten, Mark Walker, The DIRECT Consortium, Jerzy Adamski, Jochen M. Schwenk, Ewan R. Pearson, Emmanouil T. Dermitzakis, and Ana Viñuela

Subjects
Science
Abstract

Abstract We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.

Published
2023
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3. Identification of biomarkers for glycaemic deterioration in type 2 diabetes

Author

Roderick C. Slieker, Louise A. Donnelly, Elina Akalestou, Livia Lopez-Noriega, Rana Melhem, Ayşim Güneş, Frederic Abou Azar, Alexander Efanov, Eleni Georgiadou, Hermine Muniangi-Muhitu, Mahsa Sheikh, Giuseppe N. Giordano, Mikael Åkerlund, Emma Ahlqvist, Ashfaq Ali, Karina Banasik, Søren Brunak, Marko Barovic, Gerard A. Bouland, Frédéric Burdet, Mickaël Canouil, Iulian Dragan, Petra J. M. Elders, Celine Fernandez, Andreas Festa, Hugo Fitipaldi, Phillippe Froguel, Valborg Gudmundsdottir, Vilmundur Gudnason, Mathias J. Gerl, Amber A. van der Heijden, Lori L. Jennings, Michael K. Hansen, Min Kim, Isabelle Leclerc, Christian Klose, Dmitry Kuznetsov, Dina Mansour Aly, Florence Mehl, Diana Marek, Olle Melander, Anne Niknejad, Filip Ottosson, Imre Pavo, Kevin Duffin, Samreen K. Syed, Janice L. Shaw, Over Cabrera, Timothy J. Pullen, Kai Simons, Michele Solimena, Tommi Suvitaival, Asger Wretlind, Peter Rossing, Valeriya Lyssenko, Cristina Legido Quigley, Leif Groop, Bernard Thorens, Paul W. Franks, Gareth E. Lim, Jennifer Estall, Mark Ibberson, Joline W. J. Beulens, Leen M ’t Hart, Ewan R. Pearson, and Guy A. Rutter

Subjects
Science
Abstract

Abstract We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.

Published
2023
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4. Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Author

Chuanyan Wu, Yan Borné, Rui Gao, Maykel López Rodriguez, William C. Roell, Jonathan M. Wilson, Ajit Regmi, Cheng Luan, Dina Mansour Aly, Andreas Peter, Jürgen Machann, Harald Staiger, Andreas Fritsche, Andreas L. Birkenfeld, Rongya Tao, Robert Wagner, Mickaël Canouil, Mun-Gwan Hong, Jochen M. Schwenk, Emma Ahlqvist, Minna U. Kaikkonen, Peter Nilsson, Angela C. Shore, Faisel Khan, Andrea Natali, Olle Melander, Marju Orho-Melander, Jan Nilsson, Hans-Ulrich Häring, Erik Renström, Claes B. Wollheim, Gunnar Engström, Jianping Weng, Ewan R. Pearson, Paul W. Franks, Morris F. White, Kevin L. Duffin, Allan Arthur Vaag, Markku Laakso, Norbert Stefan, Leif Groop, and Yang De Marinis

Subjects
Science
Abstract

Follistatin promotes in type 2 diabetes (T2D) pathogenesis in model animals and is elevated in patients with T2D. Here the authors report that plasma follistatin associates with increased risk of incident T2D in two longitudinal cohorts, and show that follistatin regulates insulin-induced suppression lipolysis in cultured human adipocytes.

Published
2021
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5. Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference

Author

Laura J. Corbin, Vanessa Y. Tan, David A. Hughes, Kaitlin H. Wade, Dirk S. Paul, Katherine E. Tansey, Frances Butcher, Frank Dudbridge, Joanna M. Howson, Momodou W. Jallow, Catherine John, Nathalie Kingston, Cecilia M. Lindgren, Michael O’Donavan, Stephen O’Rahilly, Michael J. Owen, Colin N. A. Palmer, Ewan R. Pearson, Robert A. Scott, David A. van Heel, John Whittaker, Tim Frayling, Martin D. Tobin, Louise V. Wain, George Davey Smith, David M. Evans, Fredrik Karpe, Mark I. McCarthy, John Danesh, Paul W. Franks, and Nicholas J. Timpson

Subjects
Science
Abstract

Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.

Published
2018
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