Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels

被引：2212

作者：

Saxena, Richa

Voight, Benjamin F.

Lyssenko, Valeriya

Burtt, Noel P.

de Bakker, Paul I. W.

Chen, Hong

Roix, Jeffrey J.

Kathiresan, Sekar

Hirschhorn, Joel N.

Daly, Mark J.

Hughes, Thomas E. ^{[1
]}

Groop, Leif

Altshuler, David

Almgren, Peter

Florez, Jose C.

Meyer, Joanne

Ardlie, Kristin

Bostroem, Kristina Bengtsson

Isomaa, Bo

Lettre, Guillaume

Lindblad, Ulf

Lyon, Helen N.

Melander, Olle

Newton-Cheh, Christopher

Nilsson, Peter

Orho-Melander, Marju

Rastam, Lennart

Speliotes, Elizabeth K.

Taskinen, Marja-Riitta

Tuomi, Tiinamaija

Guiducci, Candace

Berglund, Anna

Carlson, Joyce

Gianniny, Lauren

Hackett, Rachel

Hall, Liselotte

Holmkvist, Johan

Laurila, Esa

Sjoegren, Marketa

Sterner, Maria

Surti, Aarti

Svensson, Margareta

Svensson, Malin

Tewhey, Ryan

Blumenstiel, Brendan

Parkin, Melissa

DeFelice, Matthew

Barry, Rachel

Brodeur, Wendy

Camarata, Jody

机构：

[1] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA

[2] MIT, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[8] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Diabet & Endocrinol Res Unit, Malmo, Sweden

[9] Novartis Inst Biomed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA

[10] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[11] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[12] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[13] Univ Helsinki, Univ Helsinki Hosp, Dept Med, Helsinki, Finland

[14] Skaraborg Inst, Skovde, Sweden

[15] Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland

[16] Folkhalsan Res Ctr, Helsinki, Finland

[17] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Community Med Res Unit, Malmo, Sweden

[18] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Med Res Unit, Malmo, Sweden

[19] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA

来源：

SCIENCE | 2007年 / 316卷 / 5829期

关键词：

D O I：

10.1126/science.1142358

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 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.

引用

页码：1331 / 1336

页数：6

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