Polygenic Risk Scores to Identify CVD Risk and Tailor Therapy: Hope or Hype?

被引：5

作者：

German, Charles A. ^{[1
]}

Shapiro, Michael D. ^{[1
]}

机构：

[1] Wake Forest Univ, Bowman Gray Sch Med, Ctr Prevent Cardiovasc Dis, Sect Cardiovasc Med, Winston Salem, NC 27101 USA

来源：

CURRENT ATHEROSCLEROSIS REPORTS | 2021年 / 23卷 / 09期

关键词：

Genotype; Genome-wide association study; Atherosclerosis; Cardiovascular disease; Polygenic risk score; CORONARY-HEART-DISEASE; GENETIC RISK; FAMILIAL HYPERCHOLESTEROLEMIA; CARDIOVASCULAR-DISEASE; PREDICTIVE ACCURACY; ARTERY CALCIUM; ASSOCIATION; CHOLESTEROL; PREVENTION; MUTATION;

D O I：

10.1007/s11883-021-00950-3

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Purpose of Review The purpose of this review is to understand the conceptual basis and implications of polygenic risk scores (PRS) in assessing risk of future coronary artery disease (CAD). Recent Findings Genetic information from the USA and beyond has been pooled together to create population-based biobanks, composed of millions of genotyped individuals, which have helped further our understanding of the relationship between single nucleotide polymorphisms (SNPs) and CAD. Contemporary PRS composed of millions of SNPs now serve as the gold standard and have been evaluated in several cohort studies to predict risk of CAD and potentially help guide pharmacotherapy. The development of PRS has enhanced our understanding of the relationship between genes and disease, thereby facilitating CAD risk prediction. While certain constraints currently limit their utility in clinical practice, further refinement of this tool will enable clinicians to more fully understand genetic risk and improve preventive care.

引用

页数：7

共 50 条

[1] Mutations in PCSK9 cause autosomal dominant hypercholesterolemia [J].

Abifadel, M ;

Varret, M ;

Rabès, JP ;

Allard, D ;

Ouguerram, K ;

Devillers, M ;

Cruaud, C ;

Benjannet, S ;

Wickham, L ;

Erlich, D ;

Derré, A ;

Villéger, L ;

Farnier, M ;

Beucler, I ;

Bruckert, E ;

Chambaz, J ;

Chanu, B ;

Lecerf, JM ;

Luc, G ;

Moulin, P ;

Weissenbach, J ;

Prat, A ;

Krempf, M ;

Junien, C ;

Seidah, NG ;

Boileau, C .

NATURE GENETICS, 2003, 34 (02) :154-156

[2] Genomic prediction of coronary heart disease [J].

Abraham, Gad ;

Havulinna, Aki S. ;

Bhalala, Oneil G. ;

Byars, Sean G. ;

De Livera, Alysha M. ;

Yetukuri, Laxman ;

Tikkanen, Emmi ;

Perola, Markus ;

Schunkert, Heribert ;

Sijbrands, Eric J. ;

Palotie, Aarno ;

Samani, Nilesh J. ;

Salomaa, Veikko ;

Ripatti, Samuli ;

Inouye, Michael .

EUROPEAN HEART JOURNAL, 2016, 37 (43) :3267-3278

[3]

Aragam KG, 2020, J AM COLL CARDIOL, V75, P2769, DOI 10.1016/j.jacc.2020.04.027

[4] Polygenic Scores to Assess Atherosclerotic Cardiovascular Disease Risk Clinical Perspectives and Basic Implications [J].

Aragam, Krishna G. ;

Natarajan, Pradeep .

CIRCULATION RESEARCH, 2020, 126 (09) :1159-1177

[5] The complex molecular genetics of familial hypercholesterolaemia [J].

Berberich, Amanda J. ;

Hegele, Robert A. .

NATURE REVIEWS CARDIOLOGY, 2019, 16 (01) :9-20

[6] Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque [J].

Bis, Joshua C. ;

Kavousi, Maryam ;

Franceschini, Nora ;

Isaacs, Aaron ;

Abecasis, Goncalo R. ;

Schminke, Ulf ;

Post, Wendy S. ;

Smith, Albert V. ;

Cupples, L. Adrienne ;

Markus, Hugh S. ;

Schmidt, Reinhold ;

Huffman, Jennifer E. ;

Lehtimaki, Terho ;

Baumert, Jens ;

Muenzel, Thomas ;

Heckbert, Susan R. ;

Dehghan, Abbas ;

North, Kari ;

Oostra, Ben ;

Bevan, Steve ;

Stoegerer, Eva-Maria ;

Hayward, Caroline ;

Raitakari, Olli ;

Meisinger, Christa ;

Schillert, Arne ;

Sanna, Serena ;

Voelzke, Henry ;

Cheng, Yu-Ching ;

Thorsson, Bolli ;

Fox, Caroline S. ;

Rice, Kenneth ;

Rivadeneira, Fernando ;

Nambi, Vijay ;

Halperin, Eran ;

Petrovic, Katja E. ;

Peltonen, Leena ;

Wichmann, H. Erich ;

Schnabel, Renate B. ;

Doerr, Marcus ;

Parsa, Afshin ;

Aspelund, Thor ;

Demissie, Serkalem ;

Kathiresan, Sekar ;

Reilly, Muredach P. ;

Taylor, Kent ;

Uitterlinden, Andre ;

Couper, David J. ;

Sitzer, Matthias ;

Kahonen, Mika ;

Illig, Thomas .

NATURE GENETICS, 2011, 43 (10) :940-U40

[7] Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial [J].

Damask, Amy ;

Steg, P. Gabriel ;

Schwartz, Gregory G. ;

Szarek, Michael ;

Hagstroem, Emil ;

Badimon, Lina ;

Chapman, M. John ;

Boileau, Catherine ;

Tsimikas, Sotirios ;

Ginsberg, Henry N. ;

Banerjee, Poulabi ;

Manvelian, Garen ;

Pordy, Robert ;

Hess, Sibylle ;

Overton, John D. ;

Lotta, Luca A. ;

Yancopoulos, George D. ;

Abecasis, Goncalo R. ;

Baras, Aris ;

Paulding, Charles .

CIRCULATION, 2020, 141 (08) :624-636

[8] Large-scale association analysis identifies new risk loci for coronary artery disease [J].

Deloukas, Panos ;

Kanoni, Stavroula ;

Willenborg, Christina ;

Farrall, Martin ;

Assimes, Themistocles L. ;

Thompson, John R. ;

Ingelsson, Erik ;

Saleheen, Danish ;

Erdmann, Jeanette ;

Goldstein, Benjamin A. ;

Stirrups, Kathleen ;

Koenig, Inke R. ;

Cazier, Jean-Baptiste ;

Johansson, Asa ;

Hall, Alistair S. ;

Lee, Jong-Young ;

Willer, Cristen J. ;

Chambers, John C. ;

Esko, Tonu ;

Folkersen, Lasse ;

Goel, Anuj ;

Grundberg, Elin ;

Havulinna, Aki S. ;

Ho, Weang K. ;

Hopewell, Jemma C. ;

Eriksson, Niclas ;

Kleber, Marcus E. ;

Kristiansson, Kati ;

Lundmark, Per ;

Lyytikainen, Leo-Pekka ;

Rafelt, Suzanne ;

Shungin, Dmitry ;

Strawbridge, Rona J. ;

Thorleifsson, Gudmar ;

Tikkanen, Emmi ;

Van Zuydam, Natalie ;

Voight, Benjamin F. ;

Waite, Lindsay L. ;

Zhang, Weihua ;

Ziegler, Andreas ;

Absher, Devin ;

Altshuler, David ;

Balmforth, Anthony J. ;

Barroso, Ines ;

Braund, Peter S. ;

Burgdorf, Christof ;

Claudi-Boehm, Simone ;

Cox, David ;

Dimitriou, Maria ;

Do, Ron .

NATURE GENETICS, 2013, 45 (01) :25-U52

[9] Estimation of significance thresholds for genomewide association scans [J].

Dudbridge, Frank ;

Gusnanto, Arief .

GENETIC EPIDEMIOLOGY, 2008, 32 (03) :227-234

[10] Predictive Accuracy of a Polygenic Risk Score-Enhanced Prediction Model vs a Clinical Risk Score for Coronary Artery Disease [J].

Elliott, Joshua ;

Bodinier, Barbara ;

Bond, Tom A. ;

Chadeau-Hyam, Marc ;

Evangelou, Evangelos ;

Moons, Karel G. M. ;

Dehghan, Abbas ;

Muller, David C. ;

Elliott, Paul ;

Tzoulaki, Ioanna .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (07) :636-645

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