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

VL - 40

SP - 638

EP - 645

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -