Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
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., 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., Wellcome Trust Case Control Consortium None., 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.
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.