{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:47:29Z","timestamp":1778820449896,"version":"3.51.4"},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5829","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:p>\n                    New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC\/UKT2D), we identified and confirmed three loci associated with T2D\u2014in a noncoding region near\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    and\n                    <jats:italic>CDKN2B<\/jats:italic>\n                    , in an intron of\n                    <jats:italic>IGF2BP2<\/jats:italic>\n                    , and an intron of\n                    <jats:italic>CDKAL1<\/jats:italic>\n                    \u2014and replicated associations near\n                    <jats:italic>HHEX<\/jats:italic>\n                    and in\n                    <jats:italic>SLC30A8<\/jats:italic>\n                    found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.\n                  <\/jats:p>","DOI":"10.1126\/science.1142358","type":"journal-article","created":{"date-parts":[[2007,4,26]],"date-time":"2007-04-26T21:03:40Z","timestamp":1177621420000},"page":"1331-1336","source":"Crossref","is-referenced-by-count":2285,"title":["Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels"],"prefix":"10.1126","volume":"316","author":[{"given":"Richa","family":"Saxena","sequence":"first","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Benjamin F.","family":"Voight","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Valeriya","family":"Lyssenko","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Noe\u0308l P.","family":"Burtt","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Paul I. W.","family":"de Bakker","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Jeffrey J.","family":"Roix","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Sekar","family":"Kathiresan","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, 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USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Thomas E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"Leif","family":"Groop","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}]},{"given":"David","family":"Altshuler","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA."},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Department of Molecular Biology, 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This work was supported by Novartis Institutes for BioMedical Research (D.A.) with additional support from The Richard and Susan Smith Family Foundation\/American Diabetes Association Pinnacle Program Project Award (D.A. J.N.H. M.J.D.). We thank our colleagues from the UKT2D study and the FUSION study for sharing data before publication and for close and enjoyable collaboration. We thank P. Donnelly for sharing results before publication on behalf of the WTCCC. The following are supported by NIH Research Career Awards: J.C.F. (K23 DK65978-04) H.N.L. [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K23 DK067288] NIH Research Service Award (R.S.) and a NIH Training grant award (E.K.S.). G.L. is supported by March of Dimes research grant (6-FY04-61). S.K.'s work is supported by grants from the Doris Duke Charitable Foundation the Fannie E. Rippel Foundation and NIH (grant K23-HL083102). M.J.D. D.A. S.P. and P.I.W.dB. acknowledge support from NIH\/National Heart Lung and Blood Institute (grant U01 HG004171). D.A. is a Burroughs Wellcome Fund Clinical Scholar in Translational Research and a Distinguished Clinical Scholar of the Doris Duke Charitable Foundation. L.G. T.T. B.I. M.R.T. and the Botnia Study are principally supported by the Sigrid Juselius Foundation the Finnish Diabetes Research Foundation The Folkhalsan Research Foundation and Clinical Research Institute HUCH Ltd; work in Malm\u00f6 Sweden was also funded by a Linn\u00e9 grant from the Swedish Research Council (349-2006-237). We thank H. Hilden H. Perttunen-Nio and S. Mahan for technical assistance. We thank the Botnia and Skara research teams for clinical contributions and colleagues at Massachusetts General Hospital Harvard Broad and Novartis for helpful discussions. We thank J. Avruch M. Fishman E. Lander R. Lifton and E. Scolnick for support and helpful comments on the manuscript."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1142358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:13:16Z","timestamp":1704856396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1142358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6]]},"references-count":32,"journal-issue":{"issue":"5829","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["10.1126\/science.1142358"],"URL":"https:\/\/doi.org\/10.1126\/science.1142358","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1083881.536824","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6]]}}}