Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

DSpace/Manakin Repository

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

Show simple item record

dc.contributor.author Dastani, Zari
dc.contributor.author Hivert, Marie-France
dc.contributor.author Timpson, Nicholas
dc.contributor.author Perry, John R. B.
dc.contributor.author Henneman, Peter
dc.contributor.author Heid, Iris M.
dc.contributor.author Kizer, Jorge R.
dc.contributor.author Lyytikäinen, Leo-Pekka
dc.contributor.author Fuchsberger, Christian
dc.contributor.author Tanaka, Toshiko
dc.contributor.author Morris, Andrew P.
dc.contributor.author Small, Kerrin
dc.contributor.author Isaacs, Aaron
dc.contributor.author Beekman, Marian
dc.contributor.author Coassin, Stefan
dc.contributor.author Lohman, Kurt
dc.contributor.author Kanoni, Stavroula
dc.contributor.author Pankow, James S.
dc.contributor.author Uh, Hae-Won
dc.contributor.author Bidulescu, Aurelian
dc.contributor.author Rasmussen-Torvik, Laura J.
dc.contributor.author Greenwood, Celia M. T.
dc.contributor.author Ladouceur, Martin
dc.contributor.author Grimsby, Jonna
dc.contributor.author Liu, Ching-Ti
dc.contributor.author Kooner, Jaspal
dc.contributor.author Mooser, Vincent E.
dc.contributor.author Vollenweider, Peter
dc.contributor.author Kapur, Karen A.
dc.contributor.author Chambers, John
dc.contributor.author Wareham, Nicholas J.
dc.contributor.author Langenberg, Claudia
dc.contributor.author Frants, Rune
dc.contributor.author Willems-vanDijk, Ko
dc.contributor.author Oostra, Ben A.
dc.contributor.author Willems, Sara M.
dc.contributor.author Lamina, Claudia
dc.contributor.author Winkler, Thomas W.
dc.contributor.author Psaty, Bruce M.
dc.contributor.author Tracy, Russell P.
dc.contributor.author Chen, Ida
dc.contributor.author Viikari, Jorma
dc.contributor.author Kähönen, Mika
dc.contributor.author Pramstaller, Peter P.
dc.contributor.author St. Pourcain, Beate
dc.contributor.author Sattar, Naveed
dc.contributor.author Wood, Andrew R.
dc.contributor.author Bandinelli, Stefania
dc.contributor.author Carlson, Olga D.
dc.contributor.author Egan, Josephine M.
dc.contributor.author Böhringer, Stefan
dc.contributor.author van Heemst, Diana
dc.contributor.author Kedenko, Lyudmyla
dc.contributor.author Kristiansson, Kati
dc.contributor.author Nuotio, Marja-Liisa
dc.contributor.author Loo, Britt-Marie
dc.contributor.author Harris, Tamara
dc.contributor.author Garcia, Melissa
dc.contributor.author Kanaya, Alka
dc.contributor.author Haun, Margot
dc.contributor.author Klopp, Norman
dc.contributor.author Wichmann, H.-Erich
dc.contributor.author Deloukas, Panos
dc.contributor.author Katsareli, Efi
dc.contributor.author Couper, David J.
dc.contributor.author Duncan, Bruce B.
dc.contributor.author Kloppenburg, Margreet
dc.contributor.author Adair, Linda S.
dc.contributor.author Borja, Judith B.
dc.contributor.author Wilson, James G.
dc.contributor.author Musani, Solomon
dc.contributor.author Guo, Xiuqing
dc.contributor.author Johnson, Toby
dc.contributor.author Semple, Robert
dc.contributor.author Teslovich, Tanya M.
dc.contributor.author Allison, Matthew A.
dc.contributor.author Buxbaum, Sarah G.
dc.contributor.author Mohlke, Karen L.
dc.contributor.author Meulenbelt, Ingrid
dc.contributor.author Ballantyne, Christie M.
dc.contributor.author Dedoussis, George V.
dc.contributor.author Liu, Yongmei
dc.contributor.author Paulweber, Bernhard
dc.contributor.author Spector, Timothy D.
dc.contributor.author Slagboom, P. Eline
dc.contributor.author Ferrucci, Luigi
dc.contributor.author Jula, Antti
dc.contributor.author Perola, Markus
dc.contributor.author Raitakari, Olli
dc.contributor.author Salomaa, Veikko
dc.contributor.author Eriksson, Johan G.
dc.contributor.author Frayling, Timothy M.
dc.contributor.author Hicks, Andrew A.
dc.contributor.author Lehtimäki, Terho
dc.contributor.author Siscovick, David S.
dc.contributor.author Kronenberg, Florian
dc.contributor.author van Duijn, Cornelia
dc.contributor.author Loos, Ruth J. F.
dc.contributor.author Waterworth, Dawn M.
dc.contributor.author Dupuis, Josee
dc.contributor.author Yuan, Xin
dc.contributor.author Scott, Robert A.
dc.contributor.author Qi, Lu
dc.contributor.author Wu, Ying
dc.contributor.author Manning, Alisa K
dc.contributor.author Brody, Jennifer Karen
dc.contributor.author Evans, David M.
dc.contributor.author Redline, Susan
dc.contributor.author Hu, Frank B.
dc.contributor.author Florez, Jose Carlos
dc.contributor.author Smith, George Davey
dc.contributor.author Meigs, James Benjamin
dc.contributor.author Richards, Jeremy B
dc.date.accessioned 2012-10-23T15:36:22Z
dc.date.issued 2012
dc.identifier.citation Dastani, Zari, Marie-France Hivert, Nicholas Timpson, John R. B. Perry, Xin Yuan, Robert A. Scott, Peter Henneman, et al. 2012. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals. PLoS Genetics 8(3): e1002607. en_US
dc.identifier.issn 1553-7390 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9795665
dc.description.abstract Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = \(4.5×10^{−8}–1.2×10^{−43}\)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<\(3×10^{−4}\)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = \(4.3×10^{−3}\), n = 22,044), increased triglycerides (p = \(2.6×10^{−14}\), n = 93,440), increased waist-to-hip ratio (p = \(1.8×10^{−5}\), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = \(4.4×10^{−3}\), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = \(4.5×10^{−13}\), n = 96,748) and decreased BMI (p = \(1.4×10^{−4}\), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pgen.1002607 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315470/pdf/ en_US
dash.license LAA
dc.subject biology en_US
dc.subject genetics en_US
dc.subject human genetics en_US
dc.subject molecular genetics en_US
dc.subject medicine en_US
dc.subject clinical research design en_US
dc.title Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Genetics en_US
dash.depositing.author Yuan, Xin
dc.date.available 2012-10-23T15:36:22Z

Files in this item

Files Size Format View
3315470.pdf 771.9Kb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters