Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
Voight BF., Scott LJ., Steinthorsdottir V., Morris AP., Dina C., Welch RP., Zeggini E., Huth C., Aulchenko YS., Thorleifsson G., McCulloch LJ., Ferreira T., Grallert H., Amin N., Wu G., Willer CJ., Raychaudhuri S., McCarroll SA., Langenberg C., Hofmann OM., Dupuis J., Qi L., Segrè AV., Van Hoek M., Navarro P., Ardlie K., Balkau B., Benediktsson R., Bennett AJ., Blagieva R., Boerwinkle E., Bonnycastle LL., Boström KB., Bravenboer B., Bumpstead S., Burtt NP., Charpentier G., Chines PS., Cornelis M., Couper DJ., Crawford G., Doney ASF., Elliott KS., Elliott AL., Erdos MR., Fox CS., Franklin CS., Ganser M., Gieger C., Grarup N., Green T., Griffin S., Groves CJ., Guiducci C., Hadjadj S., Hassanali N., Herder C., Isomaa B., Jackson AU., Johnson PRV., Jørgensen T., Kao WHL., Klopp N., Kong A., Kraft P., Kuusisto J., Lauritzen T., Li M., Lieverse A., Lindgren CM., Lyssenko V., Marre M., Meitinger T., Midthjell K., Morken MA., Narisu N., Nilsson P., Owen KR., Payne F., Perry JRB., Petersen AK., Platou C., Proença C., Prokopenko I., Rathmann W., Rayner NW., Robertson NR., Rocheleau G., Roden M., Sampson MJ., Saxena R., Shields BM., Shrader P., Sigurdsson G., Sparsø T., Strassburger K., Stringham HM., Sun Q., Swift AJ., Thorand B.
By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P 5 × 10 8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. © 2010 Nature America, Inc. All rights reserved.