TY - JOUR
T1 - Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
AU - Wellcome Trust Case Control Consortium
AU - For the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
AU - Zeggini, Eleftheria
AU - Scott, Laura J.
AU - Saxena, Richa
AU - Voight, Benjamin F.
AU - Marchini, Jonathan L.
AU - Hu, Tainle
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, Charles
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 - Marvelle, Amanda F.
PY - 2008/5/1
Y1 - 2008/5/1
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 ∼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 × 10-14), CDC123-CAMK1D (P = 1.2 × 10-10), TSPAN8-LGR5 (P = 1.1 × 10-9), THADA (P = 1.1 × 10-9), ADAMTS9 (P = 1.2 × 10-8) and NOTCH2 (P = 4.1 × 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 ∼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 × 10-14), CDC123-CAMK1D (P = 1.2 × 10-10), TSPAN8-LGR5 (P = 1.1 × 10-9), THADA (P = 1.1 × 10-9), ADAMTS9 (P = 1.2 × 10-8) and NOTCH2 (P = 4.1 × 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.
UR - http://www.scopus.com/inward/record.url?scp=42349106044&partnerID=8YFLogxK
U2 - 10.1038/ng.120
DO - 10.1038/ng.120
M3 - Article
C2 - 18372903
AN - SCOPUS:42349106044
SN - 1061-4036
VL - 40
SP - 638
EP - 645
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -