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

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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 Dastani, Zari Hivert, Marie-France Timpson, Nicholas Perry, John R. B. Henneman, Peter Heid, Iris M. Kizer, Jorge R. Lyytikäinen, Leo-Pekka Fuchsberger, Christian Tanaka, Toshiko Morris, Andrew P. Small, Kerrin Isaacs, Aaron Beekman, Marian Coassin, Stefan Lohman, Kurt Kanoni, Stavroula Pankow, James S. Uh, Hae-Won Bidulescu, Aurelian Rasmussen-Torvik, Laura J. Greenwood, Celia M. T. Ladouceur, Martin Grimsby, Jonna Liu, Ching-Ti Kooner, Jaspal Mooser, Vincent E. Vollenweider, Peter Kapur, Karen A. Chambers, John Wareham, Nicholas J. Langenberg, Claudia Frants, Rune Willems-vanDijk, Ko Oostra, Ben A. Willems, Sara M. Lamina, Claudia Winkler, Thomas W. Psaty, Bruce M. Tracy, Russell P. Chen, Ida Viikari, Jorma Kähönen, Mika Pramstaller, Peter P. St. Pourcain, Beate Sattar, Naveed Wood, Andrew R. Bandinelli, Stefania Carlson, Olga D. Egan, Josephine M. Böhringer, Stefan van Heemst, Diana Kedenko, Lyudmyla Kristiansson, Kati Nuotio, Marja-Liisa Loo, Britt-Marie Harris, Tamara Garcia, Melissa Kanaya, Alka Haun, Margot Klopp, Norman Wichmann, H.-Erich Deloukas, Panos Katsareli, Efi Couper, David J. Duncan, Bruce B. Kloppenburg, Margreet Adair, Linda S. Borja, Judith B. Wilson, James G. Musani, Solomon Guo, Xiuqing Johnson, Toby Semple, Robert Teslovich, Tanya M. Allison, Matthew A. Buxbaum, Sarah G. Mohlke, Karen L. Meulenbelt, Ingrid Ballantyne, Christie M. Dedoussis, George V. Liu, Yongmei Paulweber, Bernhard Spector, Timothy D. Slagboom, P. Eline Ferrucci, Luigi Jula, Antti Perola, Markus Raitakari, Olli Salomaa, Veikko Eriksson, Johan G. Frayling, Timothy M. Hicks, Andrew A. Lehtimäki, Terho Siscovick, David S. Kronenberg, Florian van Duijn, Cornelia Loos, Ruth J. F. Waterworth, Dawn M. Dupuis, Josee Yuan, Xin Scott, Robert A. Qi, Lu Wu, Ying Manning, Alisa K Brody, Jennifer Karen Evans, David M. Redline, Susan Hu, Frank B. Florez, Jose Carlos Smith, George Davey Meigs, James Benjamin Richards, Jeremy B 2012-10-23T15:36:22Z 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.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 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 Yuan, Xin 2012-10-23T15:36:22Z

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