Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci

Saxena, Richa, Elbers, Clara C., Guo, Yiran, Peter, Inga, Gaunt, Tom R., Mega, Jessica L., Lanktree, Matthew B., Tare, Archana, Castillo, Berta A., Li, Yun R., Johnson, Toby, Bruinenberg, Marcel, Gilbert-Diamond, Diane, Rajagopalan, Ramakrishnan, Voight, Benjamin F., Balasubramanyam, Ashok, Barnard, John, Bauer, Florianne, Baumert, Jens, Bhangale, Tushar, Bohm, Bernhard O., Braund, Peter S., Burton, Paul R., Chandrupatla, Hareesh R., Clarke, Robert, Cooper-Dehoff, Rhonda M., Crook, Errol D., Davey-Smith, George, Day, Ian N., de Boer, Anthonius, de Groot, Mark C. H., Drenos, Fotios, Ferguson, Jane, Fox, Caroline S., Furlong, Clement E., Gibson, Quince, Gieger, Christian, Gilhuijs-Pederson, Lisa A., Glessner, Joseph T., Goel, Anuj, Gong, Yan, Grant, Struan F. A., Grobbee, Diederick E., Hastie, Claire, Humphries, Steve E., Kim, Cecilia E., Kivimaki, Mika, Kleber, Marcus, Meisinger, Christa, Kumari, Meena, Langaee, Taimour Y., Lawlor, Debbie A., Li, Mingyao, Lobmeyer, Maximilian T., Maitland-Van Der Zee, Anke-Hilse, Meijs, Matthijs F. L., Molony, Cliona M., Morrow, David A., Murugesan, Gurunathan, Musani, Solomon K., Nelson, Christopher P., Newhouse, Stephen J., O'Connell, Jeffery R., Padmanabhan, Sandosh, Palmen, Jutta, Patel, Sanjey R., Pepine, Carl J., Pettinger, Mary, Price, Thomas S., Rafelt, Suzanne, Ranchalis, Jane, Rasheed, Asif, Rosenthal, Elisabeth, Ruczinski, Ingo, Shah, Sonia, Shen, Haiqing, Silbernagel, Gunther, Smith, Erin N., Spijkerman, Annemieke W. M., Stanton, Alice, Steffes, Michael W., Thorand, Barbara, Trip, Mieke, van der Harst, Pim, van der A, Daphne L., van Iperen, Erik P. A., van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Wolffenbuttel, Bruce H. R., Young, Taylor, Zafarmand, M. Hadi, Zmuda, Joseph M., Look AHEAD Research Group, DIAGRAM consortium, Boehnke, Michael, Altshuler, David, McCarthy, Mark, Kao, W. H. Linda, Pankow, James S., Cappola, Thomas P., Sever, Peter, Poulter, Neil, Caulfield, Mark, Dominiczak, Anna, Shields, Denis C., Bhatt, Deepak L., Zhang, Li, Curtis, Sean P., Danesh, John, Casas, Juan P., van der Schouw, Yvonne T., Onland-Moret, N. Charlotte, Doevendans, Pieter A., Dorn II, Gerald W., Farrall, Martin, FitzGerald, Garret A., Hamsten, Anders, Hegele, Robert, Hingorani, Aroon D., Hofker, Marten H., Huggins, Gordon S., Illig, Thomas, Jarvik, Gail P., Johnson, Julie A., Klungel, Olaf H., Knowler, William C., Koenig, Wolfgang, Marz, Winfried, Meigs, James B., Melander, Olle, Munroe, Patricia B., Mitchell, Braxton D., Bielinski, Susan J., Rader, Daniel J., Reilly, Muredach P, Rich, Stephen S., Rotter, Jerome I., Saleheen, Danish, Samani, Nilesh J., Schadt, Eric E., Shuldiner, Alan R., Silverstein, Roy, Kottke-Marchant, Kandice, Talmud, Philippa J., Watkins, Hugh, Asselbergs, Folkert W., de Bakker, Paul I. W., McCaffery, Jeanne, Wijmenga, Cisca, Sabatine, Marc S., Wilson, James G., Reiner, Alex, Bowden, Donald W., Hakonarson, Hakon, Siscovick, David S. and Keating, Brendan J. (2012) Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci. American Journal of Human Genetics, 90 3: 410-425. doi:10.1016/j.ajhg.2011.12.022


Author Saxena, Richa
Elbers, Clara C.
Guo, Yiran
Peter, Inga
Gaunt, Tom R.
Mega, Jessica L.
Lanktree, Matthew B.
Tare, Archana
Castillo, Berta A.
Li, Yun R.
Johnson, Toby
Bruinenberg, Marcel
Gilbert-Diamond, Diane
Rajagopalan, Ramakrishnan
Voight, Benjamin F.
Balasubramanyam, Ashok
Barnard, John
Bauer, Florianne
Baumert, Jens
Bhangale, Tushar
Bohm, Bernhard O.
Braund, Peter S.
Burton, Paul R.
Chandrupatla, Hareesh R.
Clarke, Robert
Cooper-Dehoff, Rhonda M.
Crook, Errol D.
Davey-Smith, George
Day, Ian N.
de Boer, Anthonius
de Groot, Mark C. H.
Drenos, Fotios
Ferguson, Jane
Fox, Caroline S.
Furlong, Clement E.
Gibson, Quince
Gieger, Christian
Gilhuijs-Pederson, Lisa A.
Glessner, Joseph T.
Goel, Anuj
Gong, Yan
Grant, Struan F. A.
Grobbee, Diederick E.
Hastie, Claire
Humphries, Steve E.
Kim, Cecilia E.
Kivimaki, Mika
Kleber, Marcus
Meisinger, Christa
Kumari, Meena
Langaee, Taimour Y.
Lawlor, Debbie A.
Li, Mingyao
Lobmeyer, Maximilian T.
Maitland-Van Der Zee, Anke-Hilse
Meijs, Matthijs F. L.
Molony, Cliona M.
Morrow, David A.
Murugesan, Gurunathan
Musani, Solomon K.
Nelson, Christopher P.
Newhouse, Stephen J.
O'Connell, Jeffery R.
Padmanabhan, Sandosh
Palmen, Jutta
Patel, Sanjey R.
Pepine, Carl J.
Pettinger, Mary
Price, Thomas S.
Rafelt, Suzanne
Ranchalis, Jane
Rasheed, Asif
Rosenthal, Elisabeth
Ruczinski, Ingo
Shah, Sonia
Shen, Haiqing
Silbernagel, Gunther
Smith, Erin N.
Spijkerman, Annemieke W. M.
Stanton, Alice
Steffes, Michael W.
Thorand, Barbara
Trip, Mieke
van der Harst, Pim
van der A, Daphne L.
van Iperen, Erik P. A.
van Setten, Jessica
van Vliet-Ostaptchouk, Jana V.
Verweij, Niek
Wolffenbuttel, Bruce H. R.
Young, Taylor
Zafarmand, M. Hadi
Zmuda, Joseph M.
Look AHEAD Research Group
DIAGRAM consortium
Boehnke, Michael
Altshuler, David
McCarthy, Mark
Kao, W. H. Linda
Pankow, James S.
Cappola, Thomas P.
Sever, Peter
Poulter, Neil
Caulfield, Mark
Dominiczak, Anna
Shields, Denis C.
Bhatt, Deepak L.
Zhang, Li
Curtis, Sean P.
Danesh, John
Casas, Juan P.
van der Schouw, Yvonne T.
Onland-Moret, N. Charlotte
Doevendans, Pieter A.
Dorn II, Gerald W.
Farrall, Martin
FitzGerald, Garret A.
Hamsten, Anders
Hegele, Robert
Hingorani, Aroon D.
Hofker, Marten H.
Huggins, Gordon S.
Illig, Thomas
Jarvik, Gail P.
Johnson, Julie A.
Klungel, Olaf H.
Knowler, William C.
Koenig, Wolfgang
Marz, Winfried
Meigs, James B.
Melander, Olle
Munroe, Patricia B.
Mitchell, Braxton D.
Bielinski, Susan J.
Rader, Daniel J.
Reilly, Muredach P
Rich, Stephen S.
Rotter, Jerome I.
Saleheen, Danish
Samani, Nilesh J.
Schadt, Eric E.
Shuldiner, Alan R.
Silverstein, Roy
Kottke-Marchant, Kandice
Talmud, Philippa J.
Watkins, Hugh
Asselbergs, Folkert W.
de Bakker, Paul I. W.
McCaffery, Jeanne
Wijmenga, Cisca
Sabatine, Marc S.
Wilson, James G.
Reiner, Alex
Bowden, Donald W.
Hakonarson, Hakon
Siscovick, David S.
Keating, Brendan J.
Title Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2012-03-09
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2011.12.022
Volume 90
Issue 3
Start page 410
End page 425
Total pages 16
Place of publication Cambridge, MA, United States
Publisher Cell Press
Collection year 2012
Language eng
Abstract To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10 -9) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10 -6). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10 -7) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10 -15). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10 -8). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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