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Genetic dissection ...
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Breitfeld, JanaLeipzig University
(author)
Genetic dissection of serum vaspin highlights its causal role in lipid metabolism
- Article/chapterEnglish2023
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Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:36833027-71b0-4660-aa61-c66be3b331f5
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https://lup.lub.lu.se/record/36833027-71b0-4660-aa61-c66be3b331f5URI
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https://doi.org/10.1002/oby.23882DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Objective: Vaspin (visceral adipose tissue derived serine protease inhibitor, SERPINA12) is associated with obesity-related metabolic traits, but its causative role is still elusive. The role of genetics in serum vaspin variability to establish its causal relationship with metabolically relevant traits was investigated. Methods: A meta-analysis of genome-wide association studies for serum vaspin from six independent cohorts (N = 7446) was conducted. Potential functional variants of vaspin were included in Mendelian randomization (MR) analyses to assess possible causal pathways between vaspin and homeostasis model assessment and lipid traits. To further validate the MR analyses, data from Genotype-Tissue Expression (GTEx) were analyzed, db/db mice were treated with vaspin, and serum lipids were measured. Results: A total of 468 genetic variants represented by five independent variants (rs7141073, rs1956709, rs4905216, rs61978267, rs73338689) within the vaspin locus were associated with serum vaspin (all p < 5×10−8, explained variance 16.8%). MR analyses revealed causal relationships between serum vaspin and triglycerides, low-density lipoprotein, and total cholesterol. Gene expression correlation analyses suggested that genes, highly correlated with vaspin expression in adipose tissue, are enriched in lipid metabolic processes. Finally, in vivo vaspin treatment reduced serum triglycerides in obese db/db mice. Conclusions: The data show that serum vaspin is strongly determined by genetic variants within vaspin, which further highlight vaspin's causal role in lipid metabolism.
Subject headings and genre
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Horn, KatrinLeipzig University
(author)
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Le Duc, DianaUniversity Hospital Leipzig,Max Planck Institute for Evolutionary Anthropology
(author)
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Velluva, AkhilMax Planck Institute for Evolutionary Anthropology,Leipzig University
(author)
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Marzi, CarolaGerman Center for Diabetes Research,Helmholtz Zentrum München
(author)
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Grallert, HaraldHelmholtz Zentrum München,German Center for Diabetes Research
(author)
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Friedrich, NeleGerman Centre for Cardiovascular Research,University Hospital Greifswald
(author)
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Pietzner, MaikGerman Centre for Cardiovascular Research,Berlin Institute of Health (BIH)
(author)
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Völker, UweUniversity Hospital Greifswald,German Centre for Cardiovascular Research
(author)
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Völzke, HenryUniversity Hospital Greifswald
(author)
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Ahlqvist, EmmaLund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)infl-eah
(author)
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Aly, Dina MansourLund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)di3053ma
(author)
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Tuomi, TiinamaijaLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,University of Helsinki,Helsinki University Central Hospital(Swepub:lu)ti8736tu
(author)
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Baber, RonnyLeipzig University
(author)
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Kratzsch, JürgenLeipzig University
(author)
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Thiery, JoachimUniversity of Kiel
(author)
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Isermann, BerendLeipzig University
(author)
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Loeffler, MarkusLeipzig University
(author)
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Klöting, NoraUniversity Hospital Leipzig
(author)
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Blüher, MatthiasUniversity Hospital Leipzig
(author)
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Stumvoll, MichaelGerman Center for Diabetes Research,Helmholtz Zentrum München,Leipzig University
(author)
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Heiker, John T.University Hospital Leipzig
(author)
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Tönjes, AnkeLeipzig University
(author)
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Scholz, MarkusLeipzig University
(author)
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Kovacs, PeterLeipzig University
(author)
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Leipzig UniversityUniversity Hospital Leipzig
(creator_code:org_t)
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In:Obesity31:11, s. 2862-28741930-7381
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Obesity
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Breitfeld, Jana
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Horn, Katrin
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Le Duc, Diana
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Velluva, Akhil
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Marzi, Carola
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Grallert, Harald
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Friedrich, Nele
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Pietzner, Maik
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Völker, Uwe
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Völzke, Henry
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Ahlqvist, Emma
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Aly, Dina Mansou ...
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Tuomi, Tiinamaij ...
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Baber, Ronny
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Kratzsch, Jürgen
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Thiery, Joachim
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Isermann, Berend
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Loeffler, Markus
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Klöting, Nora
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Blüher, Matthias
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Stumvoll, Michae ...
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Heiker, John T.
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Tönjes, Anke
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Scholz, Markus
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Kovacs, Peter
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Obesity
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Lund University