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Expression of phosp...
Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity.
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- Keildson, Sarah (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom,Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
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- Fadista, Joao (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
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- Ladenvall, Claes (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
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- Hedman, Åsa K (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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- Elgzyri, Targ (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Malmö, Sweden,Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
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Small, Kerrin S (författare)
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- Grundberg, Elin (författare)
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
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- Nica, Alexandra C (författare)
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
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- Glass, Daniel (författare)
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
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- Richards, J Brent (författare)
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
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- Barrett, Amy (författare)
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom
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- Nisbet, James (författare)
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Zheng, Hou-Feng (författare)
- Department of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Jewish General Hospital, Montreal, QC, Canada
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- Rönn, Tina (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
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- Ström, Kristoffer (författare)
- Mittuniversitetet,Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Avdelningen för hälsovetenskap,NVC
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- Eriksson, Karl-Fredrik (författare)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
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- Prokopenko, Inga (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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- Spector, Timothy D (författare)
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
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Dermitzakis, Emmanouil T (författare)
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- Deloukas, Panos (författare)
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- McCarthy, Mark I (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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- Rung, Johan (författare)
- European Molecular Biology Laboratory-European Bioinformatics Institute, Cambridge, United Kingdom
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- Groop, Leif (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
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- Franks, Paul (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genetisk och molekylär epidemiologi,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Genetic and Molecular Epidemiology,Department of Clinical Sciences, Genetic and Molecular Epidemiology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
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- Lindgren, Cecilia M (författare)
- Broad Institute of Massachusetts Institute of Technology, Harvard University, Cambridge, MA, USA
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- Hansson, Ola (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
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(creator_code:org_t)
- 2014-02-13
- 2014
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:3
- Relaterad länk:
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https://diabetes.dia...
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http://dx.doi.org/10...
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https://miun.diva-po... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.2...
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https://lup.lub.lu.s...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96 × 10(-5)) and 49 expression-insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment-insulin resistance, and BMI) (FDR <5%; P = 1.34 × 10(-4)). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 10(-6)) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016-0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r(2) = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7 × 10(-3)). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Diabetes
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Keildson, Sarah
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Fadista, Joao
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Ladenvall, Claes
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Hedman, Åsa K
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Elgzyri, Targ
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Small, Kerrin S
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Grundberg, Elin
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Nica, Alexandra ...
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Glass, Daniel
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Richards, J Bren ...
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Barrett, Amy
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Nisbet, James
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Zheng, Hou-Feng
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Rönn, Tina
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Ström, Kristoffe ...
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Eriksson, Karl-F ...
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Prokopenko, Inga
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Spector, Timothy ...
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Dermitzakis, Emm ...
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Deloukas, Panos
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McCarthy, Mark I
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Rung, Johan
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Groop, Leif
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Franks, Paul
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Lindgren, Cecili ...
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Hansson, Ola
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Diabetes
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