Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

Dastani, Zari, Hivert, Marie-France, Timpson, Nicholas, Perry, John R. B., Yuan, Xin, Scott, Robert A., 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, Qi, Lu, Kanoni, Stavroula, Pankow, James S., Uh, Hae-Won, Wu, Ying, Bidulescu, Aurelian, Rasmussen-Torvik, Laura J., Greenwood, Celia M. T., Ladouceur, Martin, Grimsby, Jonna, Manning, Alisa K., 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., Brody, Jennifer, Chen, Ida, Viikari, Jorma, Kähönen, Mika, Pramstaller, Peter P., Evans, David M., 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., Redline, Susan, Buxbaum, Sarah G., Mohlke, Karen L., Meulenbelt, Ingrid, Ballantyne, Christie M., Dedoussis, George V., Hu, Frank B., Liu, Yongmei, Paulweber, Bernhard, Spector, Timothy D., Slagboom, P. Eline, Ferrucci, Luigi, Jula, Antti, Perola, Markus, Raitakari, Olli, Florez, Jose C., Salomaa, Veikko, Eriksson, Johan G., Frayling, Timothy M., Hicks, Andrew A., Lehtimäki, Terho, Smith, George Davey, Siscovick, David S., Kronenberg, Florian, van Duijn, Cornelia, Loos, Ruth J. F., Waterworth, Dawn M., Meigs, James B., Dupuis, Josee, Richards, J. Brent, DIAGRAM+ Consortium, MAGIC Consortium, Coin, Lachlan J., GLGC Investigators and MuTHER Consortium (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: e1002607.1-e1002607.23. doi:10.1371/journal.pgen.1002607


Author Dastani, Zari
Hivert, Marie-France
Timpson, Nicholas
Perry, John R. B.
Yuan, Xin
Scott, Robert A.
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
Qi, Lu
Kanoni, Stavroula
Pankow, James S.
Uh, Hae-Won
Wu, Ying
Bidulescu, Aurelian
Rasmussen-Torvik, Laura J.
Greenwood, Celia M. T.
Ladouceur, Martin
Grimsby, Jonna
Manning, Alisa K.
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.
Brody, Jennifer
Chen, Ida
Viikari, Jorma
Kähönen, Mika
Pramstaller, Peter P.
Evans, David M.
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.
Redline, Susan
Buxbaum, Sarah G.
Mohlke, Karen L.
Meulenbelt, Ingrid
Ballantyne, Christie M.
Dedoussis, George V.
Hu, Frank B.
Liu, Yongmei
Paulweber, Bernhard
Spector, Timothy D.
Slagboom, P. Eline
Ferrucci, Luigi
Jula, Antti
Perola, Markus
Raitakari, Olli
Florez, Jose C.
Salomaa, Veikko
Eriksson, Johan G.
Frayling, Timothy M.
Hicks, Andrew A.
Lehtimäki, Terho
Smith, George Davey
Siscovick, David S.
Kronenberg, Florian
van Duijn, Cornelia
Loos, Ruth J. F.
Waterworth, Dawn M.
Meigs, James B.
Dupuis, Josee
Richards, J. Brent
DIAGRAM+ Consortium
MAGIC Consortium
Coin, Lachlan J.
GLGC Investigators
MuTHER Consortium
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
Journal name PloS Genetics   Check publisher's open access policy
ISSN 1553-7390
1553-7404
Publication date 2012-03-29
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1002607
Open Access Status DOI
Volume 8
Issue 3
Start page e1002607.1
End page e1002607.23
Total pages 23
Editor Peter M. Visscher
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2013
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1105 Dentistry
1306 Cancer Research
2716 Genetics (clinical)
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Institute for Molecular Bioscience - Publications
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 130 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 149 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 24 Jan 2014, 19:05:35 EST by System User on behalf of UQ Diamantina Institute