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

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 ances...

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Hauptverfasser:	Dastani, Zari, Hivert, Marie-France, Timpson, Nicholas, Henneman, Peter, Heid, Iris M, 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, Mooser, Vincent E, Kapur, Karen A, Chambers, John, 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, Kähönen, Mika, Pramstaller, Peter P, St. Pourcain, Beate, Sattar, Naveed, Wood, Andrew R, Bandinelli, Stefania, 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, 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, Buxbaum, Sarah G, Mohlke, Karen L, Meulenbelt, Ingrid, Ballantyne, Christie M, Dedoussis, George V, Liu, Yongmei, Paulweber, Bernhard, 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, 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, Hu, Frank B, Florez, Jose Carlos, Smith, George Davey, Meigs, James Benjamin, Richards, Jeremy B
Format:	Artikel
Sprache:	eng
Schlagworte:	biology clinical research design genetics human genetics medicine molecular genetics
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Zusammenfassung:	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
ISSN:	1553-7390
DOI:	10.1371/journal.pgen.1002607