Polygenic risk scores for the diagnosis and management of dyslipidemia.
Journal
Current opinion in endocrinology, diabetes, and obesity
ISSN: 1752-2978
Titre abrégé: Curr Opin Endocrinol Diabetes Obes
Pays: England
ID NLM: 101308636
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
pubmed:
17
1
2022
medline:
26
4
2022
entrez:
16
1
2022
Statut:
ppublish
Résumé
To review current progress in the use of polygenic risk scores for lipid traits and their use in the diagnosis and treatment of lipid disorders. Inherited lipid disorders, including those causing extremes of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides were initially identified as monogenic traits, in which a single rare variant with large effect size is responsible for the phenotype. More recently, a polygenic basis for many lipid traits has also been identified. Patients with polygenic dyslipidemia can be identified through the use of polygenic risk scores (PRSs), which collapse information from a handful to several million genetic variants into a single metric. PRSs for lipid traits may aid in the identification of the genetic basis for the lipid phenotype in individual patients, may provide additional information regarding the risk of cardiovascular disease, and could help in guiding therapeutic decision making.
Identifiants
pubmed: 35034034
doi: 10.1097/MED.0000000000000708
pii: 01266029-202204000-00004
doi:
Substances chimiques
Cholesterol, HDL
0
Triglycerides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
95-100Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Références
Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet 2009; 10:109–121.
Willer CJ, Sanna S, Jackson AU, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008; 40:161–169.
Kathiresan S, Melander O, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 2008; 40:189–197.
Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010; 466:707–713.
Willer CJ, Schmidt EM, Sengupta S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet 2013; 45:1274–1283.
Kathiresan S, Willer CJ, Peloso GM, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009; 41:56–65.
Trinder M, Brunham LR. Polygenic scores for dyslipidemia: the emerging genomic model of plasma lipoprotein trait inheritance. Curr Opin Lipidol 2021; 32:103–111.
Wand H, Lambert SA, Tamburro C, et al. Improving reporting standards for polygenic scores in risk prediction studies. Nature 2021; 591:211–219.
Choi SW, Mak TS, O’Reilly PF. Tutorial: a guide to performing polygenic risk score analyses. Nat Protoc 2020; 15:2759–2772.
Klarin D, Natarajan P. Clinical utility of polygenic risk scores for coronary artery disease. Nat Rev Cardiol 2021; doi: 10.1038/s41569-021-00638-w.
doi: 10.1038/s41569-021-00638-w
Kathiresan S, Melander O, Anevski D, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med 2008; 358:1240–1249.
Natarajan P, Peloso GM, Zekavat SM, et al. Deep-coverage whole genome sequences and blood lipids among 16,324 individuals. Nat Commun 2018; 9:3391.
Aragam KG, Natarajan P. Polygenic scores to assess atherosclerotic cardiovascular disease risk: clinical perspectives and basic implications. Circ Res 2020; 126:1159–1177.
Rao AS, Knowles JW. Polygenic risk scores in coronary artery disease. Curr Opin Cardiol 2019; 34:435–440.
Talmud PJ, Shah S, Whittall R, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet 2013; 381:1293–1301.
Wang J, Dron JS, Ban MR, et al. Polygenic versus monogenic causes of hypercholesterolemia ascertained clinically. Arterioscler Thromb Vasc Biol 2016; 36:2439–2445.
Trinder M, Li X, DeCastro ML, et al. Risk of premature atherosclerotic disease in patients with monogenic versus polygenic familial hypercholesterolemia. J Am Coll Cardiol 2019; 74:512–522.
Björnsson E, Thorgeirsson G, Helgadóttir A, et al. Large-scale screening for monogenic and clinically defined familial hypercholesterolemia in Iceland. Arterioscler Thromb Vasc Biol 2021; 41:2616–2628.
Trinder M, Francis GA, Brunham LR. Association of monogenic vs polygenic hypercholesterolemia with risk of atherosclerotic cardiovascular disease. JAMA Cardiol 2020; 5:390–399.
Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J 2020; 41:99c–109c.
Stahel P, Xiao C, Hegele RA, Lewis GF. Polygenic risk for hypertriglyceridemia can mimic a major monogenic mutation. Ann Intern Med 2017; 167:360–361.
Rimbert A, Vanhoye X, Coulibaly D, et al. Phenotypic differences between polygenic and monogenic hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 2021; 41:e63–e71.
Burgess S, Ference BA, Staley JR, et al. Association of LPAvariants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies. JAMA Cardiol 2018; 3:619.
Trinder M, Uddin MM, Finneran P, et al. Clinical utility of lipoprotein(a) and LPA genetic risk score in risk prediction of incident atherosclerotic cardiovascular disease. JAMA Cardiol 2021; 6:1–9.
Dron JS, Wang M, Patel AP, et al. Genetic predictor to identify individuals with high lipoprotein(a) concentrations. Circ Genom Precis Med 2021; 14:e003182.
Dron JS, Wang J, Low-Kam C, et al. Polygenic determinants in extremes of high-density lipoprotein cholesterol. J Lipid Res 2017; 58:2162–2170.
Fahed AC, Wang M, Homburger JR, et al. Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions. Nat Commun 2020; 11:3635.
Wu H, Forgetta V, Zhou S, et al. Polygenic risk score for low-density lipoprotein cholesterol is associated with risk of ischemic heart disease and enriches for individuals with familial hypercholesterolemia. Circ Genom Precis Med 2021; 14:e003106.
Paquette M, Chong M, Thériault S, et al. Polygenic risk score predicts prevalence of cardiovascular disease in patients with familial hypercholesterolemia. J Clin Lipidol 2017; 11:725.e5–732.e5.
Trinder M, Paquette M, Cermakova L, et al. Polygenic contribution to low-density lipoprotein cholesterol levels and cardiovascular risk in monogenic familial hypercholesterolemia. Circ Genom Precis Med 2020; 13:515–523.
Mega JL, Stitziel NO, Smith JG, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet 2015; 385:2264–2271.
Natarajan P, Young R, Stitziel NO, et al. Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting. Circulation 2017; 135:2091–2101.
Damask A, Steg PG, Schwartz GG, et al. 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. Circulation 2020; 141:624–636.
Marston NA, Kamanu FK, Nordio F, et al. Predicting benefit from evolocumab therapy in patients with atherosclerotic disease using a genetic risk score. Circulation 2020; 141:616–623.
Brockman DG, Petronio L, Dron JS, et al. Design and user experience testing of a polygenic score report: a qualitative study of prospective users. BMC Med Genomics 2021; 14:238.
Khera AV, Chaffin M, Wade KH, et al. Polygenic prediction of weight and obesity trajectories from birth to adulthood. Cell 2019; 177:587.e9–596.e9.
Udler MS, McCarthy MI, Florez JC, Mahajan A. Genetic risk scores for diabetes diagnosis and precision medicine. Endocr Rev 2019; 40:1500–1520.
Hegele RA, Ban MR, Hsueh N, et al. A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia. Hum Mol Genet 2009; 18:4189–4194.