Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels

Journal of the American College of Cardiology

Volumn 68, Issue 25, 2016, Pages 2761-2772

  Emdin, Connor A ^a,b   Khera, Amit V ^a,b   Natarajan, Pradeep ^a,b   Klarin, Derek ^a,b   Won, Hong Hee ^c   Peloso, Gina M ^b,d   Stitziel, Nathan O ^e   Nomura, Akihiro ^a,b   Zekavat, Seyedeh M ^a,b   Bick, Alexander G ^b   Gupta, Namrata ^b   Asselta, Rosanna ^f   Duga, Stefano ^f   Merlini, Piera Angelica ^g   Correa, Adolfo ^h   Kessler, Thorsten ^i,j   Wilson, James G ^h   Bown, Matthew J ^k   Hall, Alistair S ^l   Braund, Peter S ^k   Samani, Nilesh J ^k   Schunkert, Heribert ⁱ   Marrugat, Jaume ^m   Elosua, Roberto ^m   McPherson, Ruth ⁿ   Farrall, Martin ^o   Watkins, Hugh ^o   Willer, Cristen ^p   Abecasis, Gonçalo R ^q   Felix, Janine F ^r   Vasan, Ramachandran S ^s,t   Lander, Eric ^b   Rader, Daniel J ^u   Danesh, John ^v,w,x   Ardissino, Diego ^y,z   Gabriel, Stacey ^b   Saleheen, Danish ^aa   Kathiresan, Sekar ^a,b   more..

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c Sungkyunkwan University   (South Korea)

^d BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

^e WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^g OSPEDALE NIGUARDA CA GRANDA   (Italy)

^h UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

ⁱ TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^j Munich Heart Alliance   (Germany)

^k UNIVERSITY OF LEICESTER   (United Kingdom)

^l UNIVERSITY OF LEEDS   (United Kingdom)

^m HOSPITAL DEL MAR   (Spain)

ⁿ UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

^o UNIVERSITY OF OXFORD   (United Kingdom)

^p UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^q UNIVERSITY OF MICHIGAN SCHOOL OF PUBLIC HEALTH   (United States)

^r ERASMUS MEDICAL CENTER   (Netherlands)

^s FRAMINGHAM HEART STUDY   (United States)

^t BOSTON UNIVERSITY   (United States)

^u UNIVERSITY OF PENNSYLVANIA   (United States)

^v UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^w WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^x UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^y UNIVERSITY HOSPITAL OF PARMA   (Italy)

^z Associazione per lo Studio della Trombosi in Cardiologia   (Italy)

^aa UNIVERSITY OF PENNSYLVANIA   (United States)

more..

Author keywords

coronary heart disease; genetics; phenome wide association study; single nucleotide polymorphism

Indexed keywords

LIPOPROTEIN A; BIOLOGICAL MARKER; DNA;

AORTA STENOSIS; ARTICLE; ATHEROSCLEROSIS; CEREBROVASCULAR ACCIDENT; GENE; GENE FUNCTION; GENETIC VARIATION; HEART FAILURE; HUMAN; ISCHEMIC HEART DISEASE; LIPOPROTEIN A GENE; LIPOPROTEIN BLOOD LEVEL; MALIGNANT NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; PERIPHERAL VASCULAR DISEASE; PHENOTYPE; PRIORITY JOURNAL; RISK ASSESSMENT; BLOOD; CLINICAL TRIAL; CORONARY DISEASE; FEMALE; GENE THERAPY; GENETICS; GENOME-WIDE ASSOCIATION STUDY; MALE; MULTICENTER STUDY; PROCEDURES; PROGNOSIS; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM;

BIOMARKERS; CORONARY DISEASE; DNA; FEMALE; GENETIC THERAPY; GENOME-WIDE ASSOCIATION STUDY; HUMANS; LIPOPROTEIN(A); MALE; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROGNOSIS; RISK FACTORS;

EID: 85006411024     PISSN: 07351097     EISSN: 15583597     Source Type: Journal    
DOI: 10.1016/j.jacc.2016.10.033     Document Type: Article

References (39)

1. 1 Utermann, G., The mysteries of lipoprotein(a). Science 246 (1989), 904–910.
2. 2 Tsimikas, S., Hall, J.L., Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies. J Am Coll Cardiol 60 (2012), 716–721.
3. 3 Emerging Risk Factors Collaboration, Erqou, S., Kaptoge, S., et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 302 (2009), 412–423.
4. 4 Sandholzer, C., Saha, N., Kark, J.D., et al. Apo(a) isoforms predict risk for coronary heart disease. A study in six populations. Arterioscler Thromb 12 (1992), 1214–1226.
5. 5 Clarke, R., Peden, J.F., Hopewell, J.C., et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 361 (2009), 2518–2528.
6. 6 Kamstrup, P.R., Tybjærg-Hansen, A., Steffensen, R., Nordestgaard, B.G., Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 301 (2009), 2331–2339.
7. 7 Tsimikas, S., Viney, N.J., Hughes, S.G., et al. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet 386 (2015), 1472–1483.
8. 8 Plenge, R.M., Scolnick, E.M., Altshuler, D., Validating therapeutic targets through human genetics. Nat Rev Drug Discov 12 (2013), 581–594.
9. 9 Thanassoulis, G., Campbell, C.Y., Owens, D.S., et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 368 (2013), 503–512.
10. 10 Kamstrup, P.R., Tybjærg-Hansen, A., Nordestgaard, B.G., Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol 63 (2014), 470–477.
11. 11 Helgadottir, A., Gretarsdottir, S., Thorleifsson, G., et al. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J Am Coll Cardiol 60 (2012), 722–729.
12. 12 Hopewell, J.C., Clarke, R., Parish, S., et al. Lipoprotein(a) genetic variants associated with coronary and peripheral vascular disease but not with stroke risk in the Heart Protection Study. Circ Cardiovasc Genet 4 (2011), 68–73.
13. 13 Sawabe, M., Tanaka, N., Mieno, M.N., et al. Low lipoprotein(a) concentration is associated with cancer and all-cause deaths: a population-based cohort study (the JMS cohort study). PLoS ONE, 7, 2012, e31954.
14. 14 Mora, S., Kamstrup, P.R., Rifai, N., Nordestgaard, B.G., Buring, J.E., Ridker, P.M., Lipoprotein(a) and risk of type 2 diabetes. Clin Chem 56 (2010), 1252–1260.
15. 15 Sudlow, C., Gallacher, J., Allen, N., et al. U.K. Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med, 12, 2015, e1001779.
16. 16 International Consortium for Blood Pressure Genome-Wide Association Studies, Ehret, G.B., Munroe, P.B., et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478 (2011), 103–109.
17. 17 Global Lipids Genetics Consortium, Willer, C.J., Schmidt, E.M., et al. Discovery and refinement of loci associated with lipid levels. Nat Genet 45 (2013), 1274–1283.
18. 18 Scott, R.A., Lagou, V., Welch, R.P., et al. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet 44 (2012), 991–1005.
19. 19 CARDIoGRAMplusC4D Consortium. A comprehensive 1000 genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet 47 (2015), 1121–1130.
20. 20 Morris, A.P., Voight, B.F., Teslovich, T.M., et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44 (2012), 981–990.
21. 21 Moffatt, M.F., Gut, I.G., Demenais, F., et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363 (2010), 1211–1221.
22. 22 Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators. Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease. N Engl J Med 374 (2016), 1134–1144.
23. 23 Smith, N.L., Felix, J.F., Morrison, A.C., et al. Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. Circ Cardiovasc Genet 3 (2010), 256–266.
24. 24 Sharrett, A.R., Ballantyne, C.M., Coady, S.A., et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 104 (2001), 1108–1113.
25. 25 Chambless, L.E., McMahon, R.P., Brown, S.A., Patsch, W., Heiss, G., Shen, Y.L., Short-term intraindividual variability in lipoprotein measurements: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 136 (1992), 1069–1081.
26. 26 Virani, S.S., Brautbar, A., Davis, B.C., et al. Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 125 (2012), 241–249.
27. 27 Burgess, S., Butterworth, A., Thompson, S.G., Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol 37 (2013), 658–665.
28. 28 Do, R., Stitziel, N.O., Won, H.H., et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 518 (2015), 102–106.
29. 29 Khera, A.V., Won, H.H., Peloso, G.M., et al. Diagnostic yield of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol 67 (2016), 2578–2579.
30. 30 Kyriakou, T., Seedorf, U., Goel, A., et al. A common LPA null allele associates with lower lipoprotein(a) levels and coronary artery disease risk. Arterioscler Thromb Vasc Biol 34 (2014), 2095–2099.
31. 31 Ogorelkova, M., Gruber, A., Utermann, G., Molecular basis of congenital lp(a) deficiency: a frequent apo(a) “null” mutation in Caucasians. Hum Mol Genet 8 (1999), 2087–2096.
32. 32 Lim, E.T., Würtz, P., Havulinna, A.S., et al. Distribution and medical impact of loss-of-function variants in the Finnish founder population. PLoS Genet, 10, 2014, e1004494.
33. 33 Laschkolnig, A., Kollerits, B., Lamina, C., et al. Lipoprotein (a) concentrations, apolipoprotein (a) phenotypes, and peripheral arterial disease in three independent cohorts. Cardiovasc Res 103 (2014), 28–36.
34. 34 Chasman, D.I., Shiffman, D., Zee, R.Y., et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis 203 (2009), 371–376.
35. 35 Kettunen, J., Demirkan, A., Würtz, P., et al. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. Nat Commun, 7, 2016, 11122.
36. 36 Kraft, H.G., Lingenhel, A., Pang, R.W., et al. Frequency distributions of apolipoprotein(a) Kringle IV repeat alleles and their effects on lipoprotein(a) levels in Caucasian, Asian, and African populations: the distribution of null alleles is non-random. Eur J Hum Genet 4 (1996), 74–87.
37. 37 Shungin, D., Winkler, T.W., Croteau-Chonka, D.C., et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature 518 (2015), 187–196.
38. 38 Locke, A.E., Kahali, B., Berndt, S.I., et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 518 (2015), 197–206.
39. 39 Pattaro, C., Teumer, A., Gorski, M., et al. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nat Commun, 7, 2016, 10023.