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; Gonçalo R Abecasis; Peter Almgren; Gitte Andersen; Kristin Ardlie; Kristina Bengtsson Boström; Richard N Bergman; Lori L Bonnycastle; Knut Borch-Johnsen; Noël 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 Jørgensen; Augustine Kong; Kari Kubalanza; Finny G Kuruvilla; Johanna Kuusisto; Claudia Langenberg; Hana Lango; Torsten Lauritzen; Yun Li; Cecilia M Lindgren; Valeriya Lyssenko; Wellcome Trust Case Control Consortium; Oluf Pedersen

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, Gonçalo R Abecasis, Peter Almgren, Gitte Andersen, Kristin Ardlie, Kristina Bengtsson Boström, Richard N Bergman, Lori L Bonnycastle, Knut Borch-Johnsen, Noël 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 Jørgensen, Augustine Kong, Kari Kubalanza, Finny G Kuruvilla, Johanna Kuusisto, Claudia Langenberg, Hana Lango, Torsten Lauritzen, Yun Li, Cecilia M Lindgren, Valeriya Lyssenko, Wellcome Trust Case Control Consortium, Oluf Pedersen

1418 Citations (Scopus)

Abstract

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). 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 approximately 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.

Original language	English
Journal	Nature Genetics
Volume	40
Issue number	5
Pages (from-to)	638-45
Number of pages	7
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.120
Publication status	Published - 2008

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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., Boström, K. B., Bergman, R. N., Bonnycastle, L. L., Borch-Johnsen, K., Burtt, N. P., Chen, H., Chines, P. S., Daly, M. J., ... Pedersen, O. (2008). Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nature Genetics, 40(5), 638-45. https://doi.org/10.1038/ng.120

Zeggini, E, Scott, LJ, Saxena, R, Voight, BF, Marchini, JL, Hu, T, de Bakker, PIW, Abecasis, GR, Almgren, P, Andersen, G, Ardlie, K, Boström, 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, Jørgensen, T, Kong, A, Kubalanza, K, Kuruvilla, FG, Kuusisto, J, Langenberg, C, Lango, H, Lauritzen, T, Li, Y, Lindgren, CM, Lyssenko, V, Wellcome Trust Case Control Consortium & Pedersen, O 2008, 'Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes', Nature Genetics, vol. 40, no. 5, pp. 638-45. https://doi.org/10.1038/ng.120

@article{42d35a80ee1e11ddbf70000ea68e967b,

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). 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 approximately 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, {Gon{\c c}alo R} and Peter Almgren and Gitte Andersen and Kristin Ardlie and Bostr{\"o}m, {Kristina Bengtsson} and Bergman, {Richard N} and Bonnycastle, {Lori L} and Knut Borch-Johnsen and Burtt, {No{\"e}l 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 J{\o}rgensen 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 {Wellcome Trust Case Control Consortium} and Oluf Pedersen",

note = "Keywords: Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Genome, Human; Humans; Polymorphism, Single Nucleotide",

year = "2008",

doi = "10.1038/ng.120",

language = "English",

volume = "40",

pages = "638--45",

journal = "Nature: New biology",

issn = "1061-4036",

publisher = "nature publishing group",

number = "5",

}

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, Gonçalo R

AU - Almgren, Peter

AU - Andersen, Gitte

AU - Ardlie, Kristin

AU - Boström, Kristina Bengtsson

AU - Bergman, Richard N

AU - Bonnycastle, Lori L

AU - Borch-Johnsen, Knut

AU - Burtt, Noël 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 - Jørgensen, 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 - Wellcome Trust Case Control Consortium

AU - Pedersen, Oluf

N1 - Keywords: Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Genome, Human; Humans; Polymorphism, Single Nucleotide

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). 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 approximately 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). 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 approximately 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 - Journal article

C2 - 18372903

SN - 1061-4036

VL - 40

SP - 638

EP - 645

JO - Nature: New biology

JF - Nature: New biology

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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