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A phenome-wide comp...
A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes
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- Coral, Daniel E (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Fernandez-Tajes, Juan (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Tsereteli, Neli (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Pomares-Millan, Hugo (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Fitipaldi, Hugo (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Mutie, Pascal M (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Atabaki-Pasdar, Naeimeh (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,University of Oxford
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- Kalamajski, Sebastian (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Poveda, Alaitz (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Miller-Fleming, Tyne W (author)
- Vanderbilt University Medical Center
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- Zhong, Xue (author)
- Vanderbilt University Medical Center
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- Giordano, Giuseppe N (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Pearson, Ewan R (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,University of Dundee
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- Cox, Nancy J (author)
- University of Oxford
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- Franks, Paul W (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,Harvard T.H. Chan School of Public Health
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(creator_code:org_t)
- 2023-01-26
- 2023
- English 11 s.
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In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 5:2, s. 237-247
- Related links:
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical and molecular phenotypic layers. Key differences are identified in a wide range of traits, including cardiovascular mortality, fat distribution, liver metabolism, blood pressure, specific lipid fractions and blood levels of proteins involved in extracellular matrix remodelling. We find marginal differences in abundance of Bacteroidetes and Firmicutes bacteria in the gut. Instrumental analyses reveal prominent causal roles for waist-to-hip ratio, blood pressure and cholesterol content of high-density lipoprotein particles in the development of diabetes in obesity. We prioritize 17 genes from the discordant signature that convey protection against type 2 diabetes in obesity, which may represent logical targets for precision medicine approaches.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Genetic variation
- Machine learning
- Metabolism
- Obesity
- Type 2 diabetes
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Coral, Daniel E
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Fernandez-Tajes, ...
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Tsereteli, Neli
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Pomares-Millan, ...
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Fitipaldi, Hugo
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Mutie, Pascal M
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show more...
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Atabaki-Pasdar, ...
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Kalamajski, Seba ...
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Poveda, Alaitz
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Miller-Fleming, ...
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Zhong, Xue
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Giordano, Giusep ...
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Pearson, Ewan R
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Cox, Nancy J
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Franks, Paul W
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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Lund University