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 J.; 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 C.; 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.; Diagram+ Consortium; MAGIC Consortium; GLGC Investigators; MuTHER Consortium; Wilson, James G.; Musani, Solomon K.; Guo, Xiuqing; Johnson, Toby; Semple, Robert; Teslovich, Tanya M.; Allison, Matthew A.; Redline, Susan S.; 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. (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. PMCID: PMC3315470

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 J.; 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 C.; 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.; Diagram+ Consortium; MAGIC Consortium; GLGC Investigators; MuTHER Consortium; Wilson, James G.; Musani, Solomon K.; Guo, Xiuqing; Johnson, Toby; Semple, Robert; Teslovich, Tanya M.; Allison, Matthew A.; Redline, Susan S.; 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. (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. PMCID: PMC3315470

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Summary: Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.




JOUR



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 J.
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 C.
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.
Diagram+ Consortium
MAGIC Consortium
GLGC Investigators
MuTHER Consortium
Wilson, James G.
Musani, Solomon K.
Guo, Xiuqing
Johnson, Toby
Semple, Robert
Teslovich, Tanya M.
Allison, Matthew A.
Redline, Susan S.
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



2012


PLOS Genetics

8

3

e1002607








PMC3315470


5333

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