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

[1]

[Anonymous], HEART DIS STROK STAT

[2] Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts [J].

Aulchenko, Yurii S. ;

Ripatti, Samuli ;

Lindqvist, Ida ;

Boomsma, Dorret ;

Heid, Iris M. ;

Pramstaller, Peter P. ;

Penninx, Brenda W. J. H. ;

Janssens, A. Cecile J. W. ;

Wilson, James F. ;

Spector, Tim ;

Martin, Nicholas G. ;

Pedersen, Nancy L. ;

Kyvik, Kirsten Ohm ;

Kaprio, Jaakko ;

Hofman, Albert ;

Freimer, Nelson B. ;

Jarvelin, Marjo-Riitta ;

Gyllensten, Ulf ;

Campbell, Harry ;

Rudan, Igor ;

Johansson, Asa ;

Marroni, Fabio ;

Hayward, Caroline ;

Vitart, Veronique ;

Jonasson, Inger ;

Pattaro, Cristian ;

Wright, Alan ;

Hastie, Nick ;

Pichler, Irene ;

Hicks, Andrew A. ;

Falchi, Mario ;

Willemsen, Gonneke ;

Hottenga, Jouke-Jan ;

de Geus, Eco J. C. ;

Montgomery, Grant W. ;

Whitfield, John ;

Magnusson, Patrik ;

Saharinen, Juha ;

Perola, Markus ;

Silander, Kaisa ;

Isaacs, Aaron ;

Sijbrands, Eric J. G. ;

Uitterlinden, Andre G. ;

Witteman, Jacqueline C. M. ;

Oostra, Ben A. ;

Elliott, Paul ;

Ruokonen, Aimo ;

Sabatti, Chiara ;

Gieger, Christian ;

Meitinger, Thomas .

NATURE GENETICS, 2009, 41 (01) :47-55

[3] Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis [J].

Chasman, Daniel I. ;

Pare, Guillaume ;

Mora, Samia ;

Hopewell, Jemma C. ;

Peloso, Gina ;

Clarke, Robert ;

Cupples, L. Adrienne ;

Hamsten, Anders ;

Kathiresan, Sekar ;

Maelarstig, Anders ;

Ordovas, Jose M. ;

Ripatti, Samuli ;

Parker, Alex N. ;

Miletich, Joseph P. ;

Ridker, Paul M. .

PLOS GENETICS, 2009, 5 (11)

[4] HIGH-DENSITY LIPOPROTEIN AS A PROTECTIVE FACTOR AGAINST CORONARY HEART-DISEASE - FRAMINGHAM STUDY [J].

GORDON, T ;

CASTELLI, WP ;

HJORTLAND, MC ;

KANNEL, WB ;

DAWBER, TR .

AMERICAN JOURNAL OF MEDICINE, 1977, 62 (05) :707-714

[5] CHOLESTEROL IN THE PREDICTION OF ATHEROSCLEROTIC DISEASE - NEW PERSPECTIVES BASED ON THE FRAMINGHAM STUDY [J].

KANNEL, WB ;

CASTELLI, WP ;

GORDON, T .

ANNALS OF INTERNAL MEDICINE, 1979, 90 (01) :85-91

[6] Common variants at 30 loci contribute to polygenic dyslipidemia [J].

Kathiresan, Sekar ;

Willer, Cristen J. ;

Peloso, Gina M. ;

Demissie, Serkalem ;

Musunuru, Kiran ;

Schadt, Eric E. ;

Kaplan, Lee ;

Bennett, Derrick ;

Li, Yun ;

Tanaka, Toshiko ;

Voight, Benjamin F. ;

Bonnycastle, Lori L. ;

Jackson, Anne U. ;

Crawford, Gabriel ;

Surti, Aarti ;

Guiducci, Candace ;

Burtt, Noel P. ;

Parish, Sarah ;

Clarke, Robert ;

Zelenika, Diana ;

Kubalanza, Kari A. ;

Morken, Mario A. ;

Scott, Laura J. ;

Stringham, Heather M. ;

Galan, Pilar ;

Swift, Amy J. ;

Kuusisto, Johanna ;

Bergman, Richard N. ;

Sundvall, Jouko ;

Laakso, Markku ;

Ferrucci, Luigi ;

Scheet, Paul ;

Sanna, Serena ;

Uda, Manuela ;

Yang, Qiong ;

Lunetta, Kathryn L. ;

Dupuis, Josee ;

de Bakker, Paul I. W. ;

O'Donnell, Christopher J. ;

Chambers, John C. ;

Kooner, Jaspal S. ;

Hercberg, Serge ;

Meneton, Pierre ;

Lakatta, Edward G. ;

Scuteri, Angelo ;

Schlessinger, David ;

Tuomilehto, Jaakko ;

Collins, Francis S. ;

Groop, Leif ;

Altshuler, David .

NATURE GENETICS, 2009, 41 (01) :56-65

[7] Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans [J].

Kathiresan, Sekar ;

Melander, Olle ;

Guiducci, Candace ;

Surti, Aarti ;

Burtt, Noel P. ;

Rieder, Mark J. ;

Cooper, Gregory M. ;

Roos, Charlotta ;

Voight, Benjamin F. ;

Havulinna, Aki S. ;

Wahlstrand, Bjorn ;

Hedner, Thomas ;

Corella, Dolores ;

Tai, E. Shyong ;

Ordovas, Jose M. ;

Berglund, Goran ;

Vartiainen, Erkki ;

Jousilahti, Pekka ;

Hedblad, Bo ;

Taskinen, Marja-Riitta ;

Newton-Cheh, Christopher ;

Salomaa, Veikko ;

Peltonen, Leena ;

Groop, Leif ;

Altshuler, David M. ;

Orho-Melander, Marju .

NATURE GENETICS, 2008, 40 (02) :189-197

[8] Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants [J].

Kathiresan, Sekar ;

Altschuler, David ;

Anand, Sonia ;

Ardissino, Diego ;

Asselta, Rosanna ;

Ball, Stephen G. ;

Balmforth, Anthony J. ;

Berger, Klaus ;

Berglund, Goran ;

Bernardi, Francesco ;

Bernardinelli, Luisa ;

Berzuini, Carlo ;

Braund, Peter S. ;

Burnett, Mary-Susan ;

Burtt, Noel ;

Cambien, Francois ;

Casari, Giorgio ;

Celli, Patrizia ;

Chen, Zhen ;

Corrocher, Roberto ;

Daly, Mark J. ;

Deloukas, Panos ;

Devaney, Joe ;

Do, Ron ;

Duga, Stefano ;

Elosua, Roberto ;

Engert, James C. ;

Epstein, Stephen E. ;

Erdmann, Jeanette ;

Ferrario, Maurizio ;

Fetiveau, Raffaela ;

Fischer, Marcus ;

Friedlander, Yechiel ;

Gabriel, Stacey B. ;

Galli, Michele ;

Gianniny, Lauren ;

Girelli, Domenico ;

Grosshennig, Anika ;

Guiducci, Candace ;

Hakonarson, Hakon H. ;

Hall, Alistair S. ;

Havulinna, Aki S. ;

Hengstenberg, Christian ;

Hirschhorn, Joel N. ;

Holm, Hilma ;

Huge, Andreas ;

Kent, Kenneth M. ;

Konig, Inke R. ;

Korn, Joshua M. ;

Li, Mingyao .

NATURE GENETICS, 2009, 41 (03) :334-341

[9] High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study [J].

Kinlay, S ;

Schwartz, GG ;

Olsson, AG ;

Rifai, N ;

Leslie, SJ ;

Sasiela, WJ ;

Szarek, M ;

Libby, P ;

Ganz, P .

CIRCULATION, 2003, 108 (13) :1560-1566

[10] Complement factor H polymorphism in age-related macular degeneration [J].

Klein, RJ ;

Zeiss, C ;

Chew, EY ;

Tsai, JY ;

Sackler, RS ;

Haynes, C ;

Henning, AK ;

SanGiovanni, JP ;

Mane, SM ;

Mayne, ST ;

Bracken, MB ;

Ferris, FL ;

Ott, J ;

Barnstable, C ;

Hoh, J .

SCIENCE, 2005, 308 (5720) :385-389

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