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Mendelian randomiza...
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Yaghootkar, Hanieh
(author)
Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013-09-17
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American Diabetes Association,2013
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/196031
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https://gup.ub.gu.se/publication/196031URI
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https://doi.org/10.2337/db13-0128DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-210192URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Lamina, Claudia
(author)
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Scott, Robert A
(author)
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Dastani, Zari
(author)
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Hivert, Marie-France
(author)
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Warren, Liling L
(author)
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Stancáková, Alena
(author)
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Buxbaum, Sarah G
(author)
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Lyytikäinen, Leo-Pekka
(author)
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Henneman, Peter
(author)
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Wu, Ying
(author)
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Cheung, Chloe Y Y
(author)
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Pankow, James S
(author)
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Jackson, Anne U
(author)
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Gustafsson, StefanUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)stegu732
(author)
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Zhao, Jing Hua
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Ballantyne, Christie M
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Xie, Weijia
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Bergman, Richard N
(author)
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Boehnke, Michael
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el Bouazzaoui, Fatiha
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Collins, Francis S
(author)
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Dunn, Sandra H
(author)
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Dupuis, Josee
(author)
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Forouhi, Nita G
(author)
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Gillson, Christopher
(author)
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Hattersley, Andrew T
(author)
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Hong, Jaeyoung
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Kähönen, Mika
(author)
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Kuusisto, Johanna
(author)
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Kedenko, Lyudmyla
(author)
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Kronenberg, Florian
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Doria, Alessandro
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Assimes, Themistocles L
(author)
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Ferrannini, Ele
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Hansen, Torben
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Hao, Ke
(author)
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Häring, Hans
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Knowles, Joshua W
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Lindgren, Cecilia M
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Nolan, John J
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Paananen, Jussi
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Pedersen, Oluf
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Quertermous, Thomas
(author)
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Smith, Ulf,1943Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsmiul
(author)
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Ingelsson, ErikUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ering425
(author)
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the RISC Consortium,
(author)
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Lehtimäki, Terho
(author)
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Liu, Ching-Ti
(author)
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Loos, Ruth J F
(author)
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McCarthy, Mark I
(author)
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Morris, Andrew D
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Vasan, Ramachandran S
(author)
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Spector, Tim D
(author)
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Teslovich, Tanya M
(author)
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Tuomilehto, Jaakko
(author)
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van Dijk, Ko Willems
(author)
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Viikari, Jorma S
(author)
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Zhu, Na
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Langenberg, Claudia
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Ingelsson, Erik
(author)
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Semple, Robert K
(author)
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Sinaiko, Alan R
(author)
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Palmer, Colin N A
(author)
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Walker, Mark
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Lam, Karen S L
(author)
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Paulweber, Bernhard
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Mohlke, Karen L
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van Duijn, Cornelia
(author)
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Raitakari, Olli T
(author)
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Bidulescu, Aurelian
(author)
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Wareham, Nick J
(author)
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Laakso, Markku
(author)
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Waterworth, Dawn M
(author)
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Lawlor, Debbie A
(author)
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Meigs, James B
(author)
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Richards, J Brent
(author)
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Frayling, Timothy M
(author)
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Uppsala universitetMolekylär epidemiologi
(creator_code:org_t)
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In:Diabetes: American Diabetes Association62:10, s. 3589-35981939-327X0012-1797
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Yaghootkar, Hani ...
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Lamina, Claudia
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Scott, Robert A
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Dastani, Zari
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Hivert, Marie-Fr ...
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Warren, Liling L
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Stancáková, Alen ...
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Buxbaum, Sarah G
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Lyytikäinen, Leo ...
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Henneman, Peter
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Wu, Ying
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Cheung, Chloe Y ...
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Pankow, James S
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Jackson, Anne U
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Gustafsson, Stef ...
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Zhao, Jing Hua
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Ballantyne, Chri ...
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Xie, Weijia
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Bergman, Richard ...
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Boehnke, Michael
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el Bouazzaoui, F ...
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Collins, Francis ...
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Dunn, Sandra H
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Dupuis, Josee
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Forouhi, Nita G
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Gillson, Christo ...
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Hattersley, Andr ...
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Hong, Jaeyoung
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Kähönen, Mika
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Kuusisto, Johann ...
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Kedenko, Lyudmyl ...
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Kronenberg, Flor ...
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Doria, Alessandr ...
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Assimes, Themist ...
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Ferrannini, Ele
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Hansen, Torben
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Hao, Ke
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Häring, Hans
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Knowles, Joshua ...
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Lindgren, Cecili ...
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Nolan, John J
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Paananen, Jussi
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Pedersen, Oluf
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Quertermous, Tho ...
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Smith, Ulf, 1943
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Ingelsson, Erik
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the RISC Consort ...
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Lehtimäki, Terho
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Liu, Ching-Ti
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Loos, Ruth J F
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McCarthy, Mark I
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Morris, Andrew D
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Vasan, Ramachand ...
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Spector, Tim D
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Teslovich, Tanya ...
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Tuomilehto, Jaak ...
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van Dijk, Ko Wil ...
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Viikari, Jorma S
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Zhu, Na
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Langenberg, Clau ...
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Semple, Robert K
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Sinaiko, Alan R
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Palmer, Colin N ...
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Walker, Mark
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Lam, Karen S L
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Paulweber, Bernh ...
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Mohlke, Karen L
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van Duijn, Corne ...
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Raitakari, Olli ...
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Bidulescu, Aurel ...
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Wareham, Nick J
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Laakso, Markku
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Waterworth, Dawn ...
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Lawlor, Debbie A
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Meigs, James B
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Richards, J Bren ...
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Frayling, Timoth ...
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Diabetes
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University of Gothenburg
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Uppsala University