The shared allelic architecture of adiponectin levels and coronary artery disease

Zari Dastani; Toby Johnson; Florian Kronenberg; Christopher P Nelson; Themistocles L Assimes; Winfried März; CARDIoGRAM Consortium; ADIPOGen Consortium; J Brent Richards

doi:10.1016/j.atherosclerosis.2013.03.034

The shared allelic architecture of adiponectin levels and coronary artery disease

Atherosclerosis. 2013 Jul;229(1):145-8. doi: 10.1016/j.atherosclerosis.2013.03.034. Epub 2013 Apr 22.

Authors

Zari Dastani¹, Toby Johnson, Florian Kronenberg, Christopher P Nelson, Themistocles L Assimes, Winfried März; CARDIoGRAM Consortium; ADIPOGen Consortium; J Brent Richards

Collaborators

Sekar Kathiresan, Muredach P Reilly, Nilesh J Samani, Heribert Schunkert, Jeanette Erdmann, Themistocles L Assimes, Eric Boerwinkle, Jeanette Erdmann, Alistair Hall, Christian Hengstenberg, Sekar Kathiresan, Inke R König, Reijo Laaksonen, Ruth McPherson, Muredach P Reilly, Nilesh J Samani, Heribert Schunkert, John R Thompson, Unnur Thorsteinsdottir, Andreas Ziegler, Inke R König, John R Thompson, Devin Absher, Li Chen, L Adrienne Cupples, Eran Halperin, Mingyao Li, Kiran Musunuru, Michael Preuss, Arne Schillert, Gudmar Thorleifsson, Benjamin F Voight, George A Wells, Themistocles L Assimes, Panos Deloukas, Jeanette Erdmann, Hilma Holm, Sekar Kathiresan, Inke R König, Ruth McPherson, Muredach P Reilly, Robert Roberts, Nilesh J Samani, Heribert Schunkert, Alexandre F R Stewart, Devin Absher, Themistocles L Assimes, Stephen Fortmann, Alan Go, Mark Hlatky, Carlos Iribarren, Joshua Knowles, Richard Myers, Thomas Quertermous, Steven Sidney, Neil Risch, Hua Tang, Stefan Blankenberg, Tanja Zeller, Arne Schillert, Philipp Wild, Andreas Ziegler, Renate Schnabel, Christoph Sinning, Karl Lackner, Laurence Tiret, Viviane Nicaud, Francois Cambien, Christoph Bickel, Hans J Rupprecht, Claire Perret, Carole Proust, Thomas Münzel, Maja Barbalic, Joshua Bis, Eric Boerwinkle, Ida Yii-Der Chen, L Adrienne Cupples, Abbas Dehghan, Serkalem Demissie-Banjaw, Aaron Folsom, Nicole Glazer, Vilmundur Gudnason, Tamara Harris, Susan Heckbert, Daniel Levy, Thomas Lumley, Kristin Marciante, Alanna Morrison, Christopher J O'Donnell, Bruce M Psaty, Kenneth Rice, Jerome I Rotter, David S Siscovick, Nicholas Smith, Albert Smith, Kent D Taylor, Cornelia van Duijn, Kelly Volcik, Jaqueline Whitteman, Vasan Ramachandran, Albert Hofman, Andre Uitterlinden, Solveig Gretarsdottir, Jeffrey R Gulcher, Hilma Holm, Augustine Kong, Kari Stefansson, Gudmundur Thorgeirsson, Karl Andersen, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jeanette Erdmann, Marcus Fischer, Christian Hengstenberg, Inke R König, Wolfgang Lieb, Klaus Stark, Stefan Schreiber, H -Erich Wichmann, Andreas Ziegler, Heribert Schunkert, Zouhair Aherrahrou, Petra Bruse, Angela Doering, Jeanette Erdmann, Christian Hengstenberg, Thomas Illig, Norman Klopp, Inke R König, Christina Loley, Anja Medack, Christina Meisinger, Thomas Meitinger, Janja Nahrstaedt, Annette Peters, Klaus Stark, H -Erich Wichmann, Christina Willenborg, Andreas Ziegler, Heribert Schunkert, Bernhard O Böhm, Harald Dobnig, Tanja B Grammer, Eran Halperin, Michael M Hoffmann, Marcus Kleber, Reijo Laaksonen, Winfried März, Andreas Meinitzer, Bernhard R Winkelmann, Stefan Pilz, Wilfried Renner, Hubert Scharnagl, Tatjana Stojakovic, Andreas Tomaschitz, Karl Winkler, Benjamin F Voight, Kiran Musunuru, Candace Guiducci, Noel Burtt, Stacey B Gabriel, David S Siscovick, Christopher J O'Donnell, Roberto Elosua, Leena Peltonen, Veikko Salomaa, Stephen M Schwartz, Olle Melander, David Altshuler, Sekar Kathiresan, Alexandre F R Stewart, Li Chen, Sonny Dandona, George A Wells, Olga Jarinova, Ruth McPherson, Robert Roberts, Muredach P Reilly, Mingyao Li, Liming Qu, Robert Wilensky, William Matthai, Hakon H Hakonarson, Joe Devaney, Mary Susan Burnett, Augusto D Pichard, Kenneth M Kent, Lowell Satler, Joseph M Lindsay, Ron Waksman, Christopher W Knouff, Dawn M Waterworth, Max C Walker, Vincent Mooser, Stephen E Epstein, Daniel J Rader, Nilesh J Samani, John R Thompson, Peter S Braund, Christopher P Nelson, Benjamin J Wright, Anthony J Balmforth, Stephen G Ball, Alistair S Hall, Zari Dastani, Marie-France Hivert, Nicholas Timpson, John R B Perry, Xin Yuan, Robert A Scott, Peter Henneman, Iris M Heid, Jorge R Kizer, Leo-Pekka Lyytikäinen, Christian Fuchsberger, Toshiko Tanaka, Andrew P Morris, Kerrin Small, Aaron Isaacs, Marian Beekman, Stefan Coassin, Kurt Lohman, Lu Qi, Stavroula Kanoni, James S Pankow, Hae-Won Uh, Ying Wu, Aurelian Bidulescu, Laura J Rasmussen-Torvik, Celia M T Greenwood, Martin Ladouceur, Jonna Grimsby, Alisa K Manning, Ching-Ti Liu, Jaspal Kooner, Vincent E Mooser, Peter Vollenweider, Karen A Kapur, John Chambers, Nicholas J Wareham, Claudia Langenberg, Rune Frants, Ko Willems-vanDijk, Ben A Oostra, Sara M Willems, Claudia Lamina, Thomas W Winkler, Bruce M Psaty, Russell P Tracy, Jennifer Brody, Ida Chen, Jorma Viikari, Mika Kähönen, Peter P Pramstaller, David M Evans, Beate St Pourcain, Naveed Sattar, Andrew R Wood, Stefania Bandinelli, Olga D Carlson, Josephine M Egan, Stefan Böhringer, Diana van Heemst, Lyudmyla Kedenko, Kati Kristiansson, Marja-Liisa Nuotio, Britt-Marie Loo, Tamara Harris, Melissa Garcia, Alka Kanaya, Margot Haun, Norman Klopp, H Erich Wichmann, Panos Deloukas, Efi Katsareli, David J Couper, Bruce B Duncan, Margreet Kloppenburg, Linda S Adair, Judith B Borja, James G Wilson, Solomon Musani, Xiuqing Guo, Toby Johnson, Robert Semple, Tanya M Teslovich, Matthew A Allison, Susan Redline, Sarah G Buxbaum, Karen L Mohlke, Ingrid Meulenbelt, Christie M Ballantyne, George V Dedoussis, Frank B Hu, Yongmei Liu, Bernhard Paulweber, Timothy D Spector, P Eline Slagboom, Luigi Ferrucci, Antti Jula, Markus Perola, Olli Raitakari, Jose C Florez, Veikko Salomaa, Johan G Eriksson, Timothy M Frayling, Andrew A Hicks, Terho Lehtimäki, George Davey Smith, David S Siscovick, Florian Kronenberg, Cornelia van Duijn, Ruth J F Loos, M Waterworth, James B Meigs, Josee Dupuis, John Brent Richards

Affiliation

¹ Department of Epidemiology, Biostatistics and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University Montreal, Quebec H3T 1E2, Canada.

PMID: 23664276
PMCID: PMC6139652
DOI: 10.1016/j.atherosclerosis.2013.03.034

Abstract

Objective: A large body of epidemiologic data strongly suggests an association between excess adiposity and coronary artery disease (CAD). Low adiponectin levels, a hormone secreted only from adipocytes, have been associated with an increased risk of CAD in observational studies. However, these associations cannot clarify whether this relationship is causal or due to a shared set of causal factors or even confounding. Genome-wide association studies have identified common variants that influence adiponectin levels, providing valuable tools to examine the genetic relationship between adiponectin and CAD.

Methods: Using 145 genome wide significant SNPs for adiponectin from the ADIPOGen consortium (n = 49,891), we tested whether adiponectin-decreasing alleles influenced risk of CAD in the CARDIoGRAM consortium (n = 85,274).

Results: In single-SNP analysis, 5 variants among 145 SNPs were associated with increased risk of CAD after correcting for multiple testing (P < 4.4 × 10(-4)). Using a multi-SNP genotypic risk score to test whether adiponectin levels and CAD have a shared genetic etiology, we found that adiponectin-decreasing alleles increased risk of CAD (P = 5.4 × 10(-7)).

Conclusion: These findings demonstrate that adiponectin levels and CAD have a shared allelic architecture and provide rationale to undertake a Mendelian randomization studies to understand if this relationship is causal.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Adiponectin / genetics*
Adiposity / genetics*
Alleles
Atherosclerosis / epidemiology
Atherosclerosis / genetics
Coronary Artery Disease / epidemiology*
Coronary Artery Disease / genetics*
Databases, Genetic
Genetic Predisposition to Disease / epidemiology
Genetic Predisposition to Disease / genetics
Genome-Wide Association Study
Genotype
Humans
Male
Polymorphism, Single Nucleotide
Prevalence
Risk Factors

Substances

ADIPOQ protein, human
Adiponectin

Abstract

Publication types

MeSH terms

Substances

Grants and funding