Genome-Wide Association Studies Identify New Targets in Cardiovascular Disease

被引：15

作者：

Calkin, Anna C.

Tontonoz, Peter ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2010年 / 2卷 / 48期

关键词：

CORONARY-HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; ARTERY-DISEASE; LOCI; CHOLESTEROL; POPULATION; FRAMINGHAM; TRIGLYCERIDES; VARIANTS; MARKERS;

D O I：

10.1126/scitranslmed.3001557

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The prevalence of cardiovascular disease (CVD) continues to increase worldwide, highlighting the need for new therapeutic strategies. A recent meta-analysis of genome-wide association studies (GWASs) of over 100,000 individuals published in Nature identified 59 new loci associated with lipid traits; of these, a locus on chromosome 1p13 was most strongly associated with low-density lipoprotein cholesterol (LDL-C) levels. An accompanying study in Nature identified SORT1 as the causal gene at the 1p13 locus and showed that increased expression of sortilin-1 protein in liver was associated with lower LDL-C levels and a reduced risk of myocardial infarction. Together, these studies provide strong validation of the utility of GWASs in identifying biological pathways relevant to CVD pathogenesis and perhaps treatment.

引用

页数：4

共 25 条

[21] Biological, clinical and population relevance of 95 loci for blood lipids [J].

Teslovich, Tanya M. ;

Musunuru, Kiran ;

Smith, Albert V. ;

Edmondson, Andrew C. ;

Stylianou, Ioannis M. ;

Koseki, Masahiro ;

Pirruccello, James P. ;

Ripatti, Samuli ;

Chasman, Daniel I. ;

Willer, Cristen J. ;

Johansen, Christopher T. ;

Fouchier, Sigrid W. ;

Isaacs, Aaron ;

Peloso, Gina M. ;

Barbalic, Maja ;

Ricketts, Sally L. ;

Bis, Joshua C. ;

Aulchenko, Yurii S. ;

Thorleifsson, Gudmar ;

Feitosa, Mary F. ;

Chambers, John ;

Orho-Melander, Marju ;

Melander, Olle ;

Johnson, Toby ;

Li, Xiaohui ;

Guo, Xiuqing ;

Li, Mingyao ;

Cho, Yoon Shin ;

Go, Min Jin ;

Kim, Young Jin ;

Lee, Jong-Young ;

Park, Taesung ;

Kim, Kyunga ;

Sim, Xueling ;

Ong, Rick Twee-Hee ;

Croteau-Chonka, Damien C. ;

Lange, Leslie A. ;

Smith, Joshua D. ;

Song, Kijoung ;

Zhao, Jing Hua ;

Yuan, Xin ;

Luan, Jian'an ;

Lamina, Claudia ;

Ziegler, Andreas ;

Zhang, Weihua ;

Zee, Robert Y. L. ;

Wright, Alan F. ;

Witteman, Jacqueline C. M. ;

Wilson, James F. ;

Willemsen, Gonneke .

NATURE, 2010, 466 (7307) :707-713

[22]

Undas A, 2001, CIRCULATION, V103, P2248

[23] Genome-wide association study identifies genes for biomarkers of cardiovascular disease: Serum urate and dyslipiclemia [J].

Wallace, Chris ;

Newhouse, Stephen J. ;

Braund, Peter ;

Zhang, Feng ;

Tobin, Martin ;

Falchi, Mario ;

Ahmadi, Kourosh ;

Dobson, Richard J. ;

Maracano, Ana Carolina B. ;

Hajat, Cother ;

Burton, Paul ;

Deloukas, Panagiotis ;

Brown, Morris ;

Connell, John M. ;

Dominiczak, Anna ;

Lathrop, G. Mark ;

Webster, John ;

Farrall, Martin ;

Spector, Tim ;

Samani, Nilesh J. ;

Caulfield, Mark J. ;

Munroe, Patricia B. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (01) :139-149

[24] Newly identified loci that influence lipid concentrations and risk of coronary artery disease [J].

Willer, Cristen J. ;

Sanna, Serena ;

Jackson, Anne U. ;

Scuteri, Angelo ;

Bonnycastle, Lori L. ;

Clarke, Robert ;

Heath, Simon C. ;

Timpson, Nicholas J. ;

Najjar, Samer S. ;

Stringham, Heather M. ;

Strait, James ;

Duren, William L. ;

Maschio, Andrea ;

Busonero, Fabio ;

Mulas, Antonella ;

Albai, Giuseppe ;

Swift, Amy J. ;

Morken, Mario A. ;

Narisu, Narisu ;

Bennett, Derrick ;

Parish, Sarah ;

Shen, Haiqing ;

Galan, Pilar ;

Meneton, Pierre ;

Hercberg, Serge ;

Zelenika, Diana ;

Chen, Wei-Min ;

Li, Yun ;

Scott, Laura J. ;

Scheet, Paul A. ;

Sundvall, Jouko ;

Watanabe, Richard M. ;

Nagaraja, Ramaiah ;

Ebrahim, Shah ;

Lawlor, Debbie A. ;

Ben-Shlomo, Yoav ;

Davey-Smith, George ;

Shuldiner, Alan R. ;

Collins, Rory ;

Bergman, Richard N. ;

Uda, Manuela ;

Tuomilehto, Jaakko ;

Cao, Antonio ;

Collins, Francis S. ;

Lakatta, Edward ;

Lathrop, G. Mark ;

Boehnke, Michael ;

Schlessinger, David ;

Mohlke, Karen L. ;

Abecasis, Goncalo R. .

NATURE GENETICS, 2008, 40 (02) :161-169

[25] LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor [J].

Zelcer, Noam ;

Hong, Cynthia ;

Boyadjian, Rima ;

Tontonoz, Peter .

SCIENCE, 2009, 325 (5936) :100-104

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