Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Eleftheria Zeggini; Laura J. Scott; Richa Saxena; Benjamin F. Voight; Jonathan L. Marchini; Tianle Hu; Paul I. W. de Bakker; Goncalo R. Abecasis; Peter Almgren; Gitte Andersen; Kristin Ardlie; Kristina Bengtsson Bostroem; Richard N. Bergman; Lori L. Bonnycastle; Knut Borch-Johnsen; Noel P. Burtt; Hong Chen; Peter S. Chines; Mark J. Daly; Parimal Deodhar; Chia-Jen Ding; Alex S. F. Doney; William L. Duren; Katherine S. Elliott; Michael R. Erdos; Timothy M. Frayling; Rachel M. Freathy; Lauren Gianniny; Harald Grallert; Niels Grarup; Christopher J. Groves; Candace Guiducci; Torben Hansen; Christian Herder; Graham A. Hitman; Thomas E. Hughes; Bo Isomaa; Anne U. Jackson; Torben Jorgensen; Augustine Kong; Kari Kubalanza; Finny G. Kuruvilla; Johanna Kuusisto; Claudia Langenberg; Hana Lango; Torsten Lauritzen; Yun Li; Cecilia M. Lindgren; Valeriya Lyssenko; Amanda F. Marvelle; Christa Meisinger; Kristian Midthjell; Karen L. Mohlke; Mario A. Morken; Andrew D. Morris; Narisu Narisu; Peter Nilsson; Katharine R. Owen; Colin N. A. Palmer; Felicity Payne; John R. B. Perry; Elin Pettersen; Carl Platou; Inga Prokopenko; Lu Qi; Li Qin; Nigel W. Rayner; Matthew Rees; Jeffrey J. Roix; Anelli Sandbaek; Beverley Shields; Marketa Sjögren; Valgerdur Steinthorsdottir; Heather M. Stringham; Amy J. Swift; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Nicholas J. Timpson; Tiinamaija Tuomi; Jaakko Tuomilehto; Mark Walker; Richard M. Watanabe; Michael N. Weedon; Cristen J. Willer; Thomas Illig; Kristian Hveem; Frank B. Hu; Markku Laakso; Kari Stefansson; Oluf Pedersen; Nicholas J. Wareham; Ines Barroso; Andrew T. Hattersley; Francis S. Collins; Leif Groop; Mark I. McCarthy; Michael Boehnke; David Altshuler

doi:10.1038/ng.120

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Eleftheria Zeggini, Laura J. Scott, Richa Saxena, Benjamin F. Voight, Jonathan L. Marchini, Tianle Hu, Paul I. W. de Bakker, Goncalo R. Abecasis, Peter Almgren, Gitte Andersen, Kristin Ardlie, Kristina Bengtsson Bostroem, Richard N. Bergman, Lori L. Bonnycastle, Knut Borch-Johnsen, Noel P. Burtt, Hong Chen, Peter S. Chines, Mark J. Daly, Parimal DeodharChia-Jen Ding, Alex S. F. Doney, William L. Duren, Katherine S. Elliott, Michael R. Erdos, Timothy M. Frayling, Rachel M. Freathy, Lauren Gianniny, Harald Grallert, Niels Grarup, Christopher J. Groves, Candace Guiducci, Torben Hansen, Christian Herder, Graham A. Hitman, Thomas E. Hughes, Bo Isomaa, Anne U. Jackson, Torben Jorgensen, Augustine Kong, Kari Kubalanza, Finny G. Kuruvilla, Johanna Kuusisto, Claudia Langenberg, Hana Lango, Torsten Lauritzen, Yun Li, Cecilia M. Lindgren, Valeriya Lyssenko, Amanda F. Marvelle, Christa Meisinger, Kristian Midthjell, Karen L. Mohlke, Mario A. Morken, Andrew D. Morris, Narisu Narisu, Peter Nilsson, Katharine R. Owen, Colin N. A. Palmer, Felicity Payne, John R. B. Perry, Elin Pettersen, Carl Platou, Inga Prokopenko, Lu Qi, Li Qin, Nigel W. Rayner, Matthew Rees, Jeffrey J. Roix, Anelli Sandbaek, Beverley Shields, Marketa Sjögren, Valgerdur Steinthorsdottir, Heather M. Stringham, Amy J. Swift, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Nicholas J. Timpson, Tiinamaija Tuomi, Jaakko Tuomilehto, Mark Walker, Richard M. Watanabe, Michael N. Weedon, Cristen J. Willer, Thomas Illig, Kristian Hveem, Frank B. Hu, Markku Laakso, Kari Stefansson, Oluf Pedersen, Nicholas J. Wareham, Ines Barroso, Andrew T. Hattersley, Francis S. Collins, Leif Groop, Mark I. McCarthy, Michael Boehnke, David Altshuler

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Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

Originalspråk	engelska
Sidor (från-till)	638-645
Tidskrift	Nature Genetics
Volym	40
Nummer	5
DOI	https://doi.org/10.1038/ng.120
Status	Published - 2008

Ämnesklassifikation (UKÄ)

Endokrinologi och diabetes

FN:s Globala mål

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10.1038/ng.120

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Zeggini, E., Scott, L. J., Saxena, R., Voight, B. F., Marchini, J. L., Hu, T., de Bakker, P. I. W., Abecasis, G. R., Almgren, P., Andersen, G., Ardlie, K., Bostroem, K. B., Bergman, R. N., Bonnycastle, L. L., Borch-Johnsen, K., Burtt, N. P., Chen, H., Chines, P. S., Daly, M. J., ... Altshuler, D. (2008). Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nature Genetics, 40(5), 638-645. https://doi.org/10.1038/ng.120

@article{00e89a107f604524a7d1d2ac0ae49eeb,

title = "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes",

abstract = "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.",

author = "Eleftheria Zeggini and Scott, {Laura J.} and Richa Saxena and Voight, {Benjamin F.} and Marchini, {Jonathan L.} and Tianle Hu and {de Bakker}, {Paul I. W.} and Abecasis, {Goncalo R.} and Peter Almgren and Gitte Andersen and Kristin Ardlie and Bostroem, {Kristina Bengtsson} and Bergman, {Richard N.} and Bonnycastle, {Lori L.} and Knut Borch-Johnsen and Burtt, {Noel P.} and Hong Chen and Chines, {Peter S.} and Daly, {Mark J.} and Parimal Deodhar and Chia-Jen Ding and Doney, {Alex S. F.} and Duren, {William L.} and Elliott, {Katherine S.} and Erdos, {Michael R.} and Frayling, {Timothy M.} and Freathy, {Rachel M.} and Lauren Gianniny and Harald Grallert and Niels Grarup and Groves, {Christopher J.} and Candace Guiducci and Torben Hansen and Christian Herder and Hitman, {Graham A.} and Hughes, {Thomas E.} and Bo Isomaa and Jackson, {Anne U.} and Torben Jorgensen and Augustine Kong and Kari Kubalanza and Kuruvilla, {Finny G.} and Johanna Kuusisto and Claudia Langenberg and Hana Lango and Torsten Lauritzen and Yun Li and Lindgren, {Cecilia M.} and Valeriya Lyssenko and Marvelle, {Amanda F.} and Christa Meisinger and Kristian Midthjell and Mohlke, {Karen L.} and Morken, {Mario A.} and Morris, {Andrew D.} and Narisu Narisu and Peter Nilsson and Owen, {Katharine R.} and Palmer, {Colin N. A.} and Felicity Payne and Perry, {John R. B.} and Elin Pettersen and Carl Platou and Inga Prokopenko and Lu Qi and Li Qin and Rayner, {Nigel W.} and Matthew Rees and Roix, {Jeffrey J.} and Anelli Sandbaek and Beverley Shields and Marketa Sj{\"o}gren and Valgerdur Steinthorsdottir and Stringham, {Heather M.} and Swift, {Amy J.} and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Timpson, {Nicholas J.} and Tiinamaija Tuomi and Jaakko Tuomilehto and Mark Walker and Watanabe, {Richard M.} and Weedon, {Michael N.} and Willer, {Cristen J.} and Thomas Illig and Kristian Hveem and Hu, {Frank B.} and Markku Laakso and Kari Stefansson and Oluf Pedersen and Wareham, {Nicholas J.} and Ines Barroso and Hattersley, {Andrew T.} and Collins, {Francis S.} and Leif Groop and McCarthy, {Mark I.} and Michael Boehnke and David Altshuler",

year = "2008",

doi = "10.1038/ng.120",

language = "English",

volume = "40",

pages = "638--645",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Publishing Group",

number = "5",

}

Zeggini, E, Scott, LJ, Saxena, R, Voight, BF, Marchini, JL, Hu, T, de Bakker, PIW, Abecasis, GR, Almgren, P, Andersen, G, Ardlie, K, Bostroem, KB, Bergman, RN, Bonnycastle, LL, Borch-Johnsen, K, Burtt, NP, Chen, H, Chines, PS, Daly, MJ, Deodhar, P, Ding, C-J, Doney, ASF, Duren, WL, Elliott, KS, Erdos, MR, Frayling, TM, Freathy, RM, Gianniny, L, Grallert, H, Grarup, N, Groves, CJ, Guiducci, C, Hansen, T, Herder, C, Hitman, GA, Hughes, TE, Isomaa, B, Jackson, AU, Jorgensen, T, Kong, A, Kubalanza, K, Kuruvilla, FG, Kuusisto, J, Langenberg, C, Lango, H, Lauritzen, T, Li, Y, Lindgren, CM, Lyssenko, V, Marvelle, AF, Meisinger, C, Midthjell, K, Mohlke, KL, Morken, MA, Morris, AD, Narisu, N, Nilsson, P, Owen, KR, Palmer, CNA, Payne, F, Perry, JRB, Pettersen, E, Platou, C, Prokopenko, I, Qi, L, Qin, L, Rayner, NW, Rees, M, Roix, JJ, Sandbaek, A, Shields, B, Sjögren, M, Steinthorsdottir, V, Stringham, HM, Swift, AJ, Thorleifsson, G, Thorsteinsdottir, U, Timpson, NJ, Tuomi, T, Tuomilehto, J, Walker, M, Watanabe, RM, Weedon, MN, Willer, CJ, Illig, T, Hveem, K, Hu, FB, Laakso, M, Stefansson, K, Pedersen, O, Wareham, NJ, Barroso, I, Hattersley, AT, Collins, FS, Groop, L, McCarthy, MI, Boehnke, M & Altshuler, D 2008, 'Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes', Nature Genetics, vol. 40, nr. 5, s. 638-645. https://doi.org/10.1038/ng.120

TY - JOUR

T1 - Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

AU - Zeggini, Eleftheria

AU - Scott, Laura J.

AU - Saxena, Richa

AU - Voight, Benjamin F.

AU - Marchini, Jonathan L.

AU - Hu, Tianle

AU - de Bakker, Paul I. W.

AU - Abecasis, Goncalo R.

AU - Almgren, Peter

AU - Andersen, Gitte

AU - Ardlie, Kristin

AU - Bostroem, Kristina Bengtsson

AU - Bergman, Richard N.

AU - Bonnycastle, Lori L.

AU - Borch-Johnsen, Knut

AU - Burtt, Noel P.

AU - Chen, Hong

AU - Chines, Peter S.

AU - Daly, Mark J.

AU - Deodhar, Parimal

AU - Ding, Chia-Jen

AU - Doney, Alex S. F.

AU - Duren, William L.

AU - Elliott, Katherine S.

AU - Erdos, Michael R.

AU - Frayling, Timothy M.

AU - Freathy, Rachel M.

AU - Gianniny, Lauren

AU - Grallert, Harald

AU - Grarup, Niels

AU - Groves, Christopher J.

AU - Guiducci, Candace

AU - Hansen, Torben

AU - Herder, Christian

AU - Hitman, Graham A.

AU - Hughes, Thomas E.

AU - Isomaa, Bo

AU - Jackson, Anne U.

AU - Jorgensen, Torben

AU - Kong, Augustine

AU - Kubalanza, Kari

AU - Kuruvilla, Finny G.

AU - Kuusisto, Johanna

AU - Langenberg, Claudia

AU - Lango, Hana

AU - Lauritzen, Torsten

AU - Li, Yun

AU - Lindgren, Cecilia M.

AU - Lyssenko, Valeriya

AU - Marvelle, Amanda F.

AU - Meisinger, Christa

AU - Midthjell, Kristian

AU - Mohlke, Karen L.

AU - Morken, Mario A.

AU - Morris, Andrew D.

AU - Narisu, Narisu

AU - Nilsson, Peter

AU - Owen, Katharine R.

AU - Palmer, Colin N. A.

AU - Payne, Felicity

AU - Perry, John R. B.

AU - Pettersen, Elin

AU - Platou, Carl

AU - Prokopenko, Inga

AU - Qi, Lu

AU - Qin, Li

AU - Rayner, Nigel W.

AU - Rees, Matthew

AU - Roix, Jeffrey J.

AU - Sandbaek, Anelli

AU - Shields, Beverley

AU - Sjögren, Marketa

AU - Steinthorsdottir, Valgerdur

AU - Stringham, Heather M.

AU - Swift, Amy J.

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Timpson, Nicholas J.

AU - Tuomi, Tiinamaija

AU - Tuomilehto, Jaakko

AU - Walker, Mark

AU - Watanabe, Richard M.

AU - Weedon, Michael N.

AU - Willer, Cristen J.

AU - Illig, Thomas

AU - Hveem, Kristian

AU - Hu, Frank B.

AU - Laakso, Markku

AU - Stefansson, Kari

AU - Pedersen, Oluf

AU - Wareham, Nicholas J.

AU - Barroso, Ines

AU - Hattersley, Andrew T.

AU - Collins, Francis S.

AU - Groop, Leif

AU - McCarthy, Mark I.

AU - Boehnke, Michael

AU - Altshuler, David

PY - 2008

Y1 - 2008

N2 - Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

AB - Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

U2 - 10.1038/ng.120

DO - 10.1038/ng.120

M3 - Article

C2 - 18372903

SN - 1546-1718

VL - 40

SP - 638

EP - 645

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

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FN:s Globala mål

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