Ruddy Canadian Cardiovascular Genetics Centre

Fluids machineGenetic factors account for approximately 50% of heart disease risk. Understanding the genetics of heart disease is a major research focus in cardiovascular medicine. Knowledge of relevant genes and their function will extend our knowledge of the biological pathways that lead to heart disease. It will enable targeted prevention and treatment and will potentially result in new diagnostic tests and new therapies.

The John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre is the first comprehensive Cardiovascular Genetic Centre dedicated to both the research and clinical management of inherited cardiovascular disease in Canada.

Since the discovery of the chromosome 9p21 risk locus in 2007, we have, in collaboration with several groups around the world, identified more than 55 genomic loci that significantly alter heart disease risk.

The Centre is also home to the Genetic Analysis Core Facility which provides genotyping services, specialized equipment and technical expertise to researchers throughout the University of Ottawa Heart Institute and to external researchers internationally and to the Statistical Genetics Services.


Identification of common and rare genetic variants that increase the risk for coronary artery disease

This is a large genome-wide association study (over 12,000 participants), under the direction of Dr. Ruth McPherson, with the support of operating grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation. Patients with early onset coronary artery disease and healthy elderly individuals consent to have their genetic variants screened using the high capacity Affymetrix genotyping platforms. As part of this study and in collaboration with groups around the world, we have identified 57 novel genetic risk factors that contribute to coronary artery disease risk. Most of these are not related to known risk factors for CAD such as hypercholesterolemia, hypertension and diabetes and thus have provided new knowledge regarding the complex biological pathways that lead to this common disease.

We have furthered this knowledge in several ways: 

  1. We have obtained novel insights into the genetic architecture of CAD by interpreting these genetic findings in the context of biological processes and functional interactions among genes, a “systems genetics approach”.  
  2. As part of a collaboration amongst Oxford University, the Broad Institute and our group, we have made use of the 1000 Genomes sequencing data to interrogate a much larger number of informative SNPs (common genetic variants).  This has allowed us to address an unanswered question in human cardiovascular genetics that is the relative importance of rare genetic variants with a high effect size versus multiple common variants of small effect size.  We have recently reported that the latter paradigm is correct (Nature Genetics 2015). 
  3. A major and important focus of our respective laboratories (Drs. Stewart & McPherson) is identifying the functional relationship of newly identified genetic variants to CAD.  This work has resulted in new insights into the biology underlying multiple CAD risk loci including 9p21, SPG7, COL4A1/4A2, SMAD3, TRIB1 and ZC3HC1 and has highlighted an important role for cell proliferation in vascular smooth muscle cells. 
  4. Using a Mendelian randomization approach, we have been able to conclude that obesity, hypertension, elevated levels of LDL-cholesterol and triglycerides are causative risk factors for CAD unlike markers of CAD risk including blood levels of HDL-cholesterol and C-reactive protein.
  5. Analysis of the statistical interaction a) between genetic variants (epistasis) and b) between genetic variants and the environment has also provided new information that can identify patients for whom weight loss or smoking cessation are particularly important. 
  6. Finally, creation of a genetic risk score for CAD based on the number and effect size of the multiple risk variants identified has proved useful in identifying individuals for whom earlier application of various risk deferring therapies such as statin treatment of blood pressure lowering is indicated.

The importance of these studies is reflected in more than 75 peer reviewed papers in high impact journals including Nature, Science, Nature Genetics, Lancet and New England Journal of Medicine.

Genetic variants that predispose to salt-sensitive hypertension

This is a genome-wide association study under the direction of Dr. Frans Leenen  with support of the Canadian Institutes of Health Research. High blood pressure is a common and important risk factor for heart disease and stroke.  About 50% of people with high blood pressure are salt sensitive which means that blood pressure increases in response to high salt consumption and drops when salt in the diet is restricted. If the blood pressure does not respond to salt in the diet, the person is said to be salt resistant. There is evidence that genes contribute to salt sensitivity in people. This study seeks to determine whether individuals with a family history of early onset (before 60 years) high blood pressure are salt sensitive and identify specific genes that contribute to salt sensitivity.

Identifying genetic variants that underlie predisposition to obesity and its response to treatment

Under the direction of Dr. Ruth McPherson this study is supported by the Canadian Institutes of Health Research and uses both genome-wide approaches and targeted sequencing to identify genetic variants that contribute to the risk for becoming obese and/or alter response to treatment.



McPherson R, Tybjaerg-Hansen, A.  Genetics of Coronary Artery Disease.  Circulation Research 2016;118:564-578.

Turner AW, Martinuk A, Silva A, Lau P, Nikpay M, Eriksson P, Folkersen L, Perisic L, Hedin U, Soubeyrand S, McPherson R.  Functional Analysis of a Novel Genome-wide Association Study Signal in SMAD3 that Confers Protection from Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2016;36:972-983.

Soubeyrand S, Martinuk A, Naing T, McPherson R.  Role of Tribbles Pseudokinase 1 (TRIB1) in human hepatocyte metabolism.  BBA - Molecular Basis of Disease 2016;1862:223-232.

Cole CB, Nikpay M, Stewart AF, McPherson R.  Increased genetic risk for obesity in premature coronary artery disease”. Eur J Hum Genet. 2016;24:587-91.

So DY, Wells GA, McPherson R, Labinaz M, Le May MR, Glover C, Dick AJ, Froeschl M, Marquis JF, Gollob MH, Tran L, Bernick J, Hibbert B, Roberts JD. A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study. Pharmacogenomics J. 2016;16:71-8

Hartiala JA, Tang WH, Wang Z, Crow AL, Stewart AF, Roberts R, McPherson R, Erdmann J, Willenborg C,Hazen SL, Allayee H. Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease. Nat Commun. 2016; 7:10558.

Stitziel NO, Stirrups KE, Masca NG, Erdmann J, Ferrario PG, König IR, Weeke PE, Webb TR, Auer PL, Schick UM, Lu Y, Zhang H, Dube MP, Goel A, Farrall M, Peloso GM, Won HH, Do R, van Iperen E, Kanoni S, Kruppa J, Mahajan A, Scott RA, Willenborg C, Braund PS, van Capelleveen JC,Doney AS, Donnelly LA, Asselta R, Merlini PA, Duga S, Marziliano N, Denny JC, Shaffer CM, El-Mokhtari NE, Franke A, Gottesman O, Heilmann S,Hengstenberg C, Hoffmann P, Holmen OL, Hveem K, Jansson JH, Jöckel KH, Kessler T, Kriebel J, Laugwitz KL, Marouli E, Martinelli N, McCarthy MI, Van Zuydam NR, Meisinger C, Esko T, Mihailov E, Escher SA, Alver M, Moebus S, Morris AD, Müller-Nurasyid M, Nikpay M, Olivieri O, Perreault LP, AlQarawi A, Robertson NR, Akinsanya KO, Reilly DF, Vogt TF, Yin W, Asselbergs FW, Kooperberg C, Jackson RD, Stahl E, Strauch K, Varga TV, Waldenberger M, Zeng L, Kraja AT, Liu C, Ehret GB, Newton-Cheh C, Chasman DI, Chowdhury R, Ferrario M, Ford I, Jukema J, Kee F,Kuulasmaa K, Nordestgaard BG, Perola M, Saleheen D, Sattar N, Surendran P, Tregouet D, Young R, Howson JM, Butterworth AS, Danesh J,Ardissino D, Bottinger EP, Erbel R, Franks PW, Girelli D, Hall AS, Hovingh G, Kastrati A, Lieb W, Meitinger T, Kraus WE, Shah SH, McPherson R,Orho-Melander M, Melander O, Metspalu A, Palmer CN, Peters A, Rader DJ, Reilly MP, Loos RJ, Reiner AP, Roden DM, Tardif JC, Thompson JR,Wareham NJ, Watkins H, Willer CJ, Kathiresan S, Deloukas P, Samani NJ, Schunkert H. 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. 2016;374:1134-44.

Golbus JR, Stitziel NO, Zhao W, Xue C, Farrall M, McPherson R, Erdmann J, Deloukas P, Watkins H, Schunkert H, Samani NJ, Saleheen D, Kathiresan S, Reilly MP. Common and Rare Genetic Variation in CCR2, CCR5, or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits. Circ Cardiovasc Genet. 2016;9:250-8.

Soubeyrand S, Martinuk A, Lau P, McPherson R. TRIB1 Is Regulated Post-Transcriptionally by Proteasomal and Non-Proteasomal Pathways. PLoS One. 2016;28,11(3):e0152346.

Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, van Leeuwen EM, Natarajan P, Emdin CA, Bick AG, Morrison AC, Brody JA, Gupta N, Nomura A, Kessler T, Duga S, Bis JC, van Duijn CM, Cupples LA, Psaty B, Rader DJ, Danesh J, Schunkert H, McPherson R, Farrall M, Watkins H, Lander E, Wilson JG, Correa A, Boerwinkle E, Merlini PA, Ardissino D, Saleheen D, Gabriel S, Kathiresan S. Diagnostic Yield of Sequencing Familial Hypercholesterolemia Genes in Patients with Severe Hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578-89.



Chen HH, Keyhanian K, Zhou X, Vilmundarson RO, Almontashiri NA, Cruz S, Pandey NR, Yap NL, Ho T, Stewart CA, Huang H, Hari A, Geoffrion M, McPherson R, Rayner KJ, Stewart AF. IRF2BP2 reduces macrophage inflammation and susceptibility to atherosclerosis. Circ Res. 2015;117:671-83.

Nikpay M, Goel A, Won HH, Hall LM, Willenborg C, Kanoni S, Saleheen D, Kyriakou T, Nelson CP, Hopewell JC, Webb TR, Zeng L, Dehghan A, Alver M, Armasu SM, Auro K, Bjonnes A, Chasman DI, Chen S, Ford I, Franceschini N, Gieger C, Grace C, Gustafsson S, Huang J, Hwang SJ, Kim YK, Kleber ME, Lau KW, Lu Y, Lu X, Lyytikäinen LP, Mihailov[ E, Morrison A, Pervjakova N, Qu L, Rose LM, Salfati[ E, Saxena[ R, Scholz M, Smith AV, Tikkanen E, Uitterlinden A, Yang X, Zhang W, Zhao W, de Andrade M, de Vries PS, van Zuydam NR, Anand SS, Bertram L, Beutner F, Dedoussis G, Frossard P, Gauguier D, Goodall AH, Gottesman O, Haber M, Han BG, Huang J, Jalilzadeh S], Kessler T, R König IR, Lannfelt L, Lieb W, Lind L, Lindgren CM, Lokki M, Magnusson PK, Mallick NH, Mehra N, Meitinger T, Memon F, Morris AP,   Nieminen MS, Pedersen  NL, Peters A, Rallidis LS,  Rasheed A, Samuel M, Shah SH,  Sinisalo J, Stirrups KE, Trompet S, Wang L,   Zaman KS, Ardissino D,  Boerwinkle E, Borecki IB, Bottinger EP, Buring JE, Chambers JC,  Collins R, Cupples LA, Danesh J, Elosua R, Epstein SE, Esko T,   Feitosa MF, Franco OH,   Franzosi MG, Granger CB, Gu D, Gudnason V, Hall AS, Hamsten A, Harris TB, Hazen SL, Hengstenberg C, Hofman A, Ingelsson E, Iribarren C, Jukema JW, Karhunen PJ, Kim BJ, Kooner JS, Kullo IJ, Lehtimäki T, Loos RJ, Melander O, Metspalu A, März W, Palmer CN, Perola M, Quertermous T, Rader DJ, Ridker PM, Ripatti S, Roberts R, Salomaa V, Sanghera DK, Schwartz SM, Seedorf U, Stewart AF, Stott DJ, Thiery J, Zalloua PA, O'Donnell CJ, Reilly MP, Assimes TL, Thompson JR, Clarke R, Watkins H,  Kathiresan S, McPherson R, Deloukas P, Schunkert H, Samani NJ, Farrall M. A comprehensive 1000 genomes-based genome-wide meta-analysis of coronary artery disease.   Nature Genetics 2015; 47:1121-30.  (151 co-authors; 4 corresponding authors: M Farrell, R McPherson, S Kathiresan & H Watkins

Messaoudi S, He Y, Gutsol A, Wight A, Hébert RL, Vilmundarson RO, Makrigiannis AP, Chalmers J, Hamet P, Tremblay J, McPherson R, Stewart AF, Touyz RM, Nemer M. Endothelial Gata5 transcription factor regulates blood pressure.Nat Commun. 2015;6:8835.

Do, R, Stitziel NO, Jørgensen AB, Duga S, Merlini PA, Kiezun A, Won HH, Farrall M, Goel A, Guella I, Asselta R, Lange LA, Peloso GM, Auer PL, NHLBI Exome Sequencing Project, Girelli D, Martinelli N, Farlow DN, DePristo MA, Roberts R, Stewart AFR, Saleheen D, Danesh J, Epstein SE, Sivapalaratnam S, Hovingh GK, Kastelein JJ, Samani NJ, Schunkert H, Erdmann J, Shah S, Kraus WE, Davies RW, Nikpay M, Johansen CT, Wang J, Hegele RA, Zuk O, Hechter E, Marz W, Kleber ME, Huang J, Johnson AD,  Li m, Burke G, Gross M, Liu y, Assimes TL, Heiss G, Lange EM, Folsom AR, Taylor HA, Olivieri O, Hamsten A, Clarke R, Rivas MA, Donnelly P, Rossouw JE, Psaty BM, Herrington DM, Wilson JG, Rich SS,  Bamshad MJ, Tracy RP, Cupples LA, Rader DJ, Reilly MP, Spertus JA, Cresci S, Hartiala J, Tang WHW, Hazen S, Allayee H, Reiner AP, Carlson CS, Kooperberg C, Jackson RD, Boerwinkle E, Lander ES, Schwartz SM, Siscovick DS, McPherson R, Tybjaerg-Hansen A, Abecasis GR, Watkins H,  Ardissino D, Nickerson DA,  Sunyaev SR, O’Donnell CJ, Altshuler D, Gabriel S, Kathiresan S.  Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.  Nature 2015;518:102-6.

Ghosh S, Vivar J, Nelson C, Willenborg C, Segre A, Makinen VP, Nikpay M, Erdmann J, Blankenberg S, O'Donnell C, März W, Laaksonen R, Stewart A, Epstein S, Shah S, Granger C, Hazen S, Kathiresan S, Reilly M, Yang X, Quertermous T, Samani N, Schunkert H, Assimes T, McPherson R. Systems Genetics Analysis of GWAS reveals Novel Associations between Key Biological Processes and Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2015;35:1712-22.

So DY, Wells GA, McPherson R, Labinaz M, Le May MR, Glover C, Dick AJ, Froeschl M, Marquis JF, Gollob MH, Tran L, Bernick J, Hibbert B, Roberts JD. A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study. Pharmacogenomics J. 2015 Apr 7.

Nelson CP, Hamby SE, Saleheen D, Hopewell JC, Zeng L, Assimes TL, Kanoni S, Willenborg C, Burgess S, Amouyel P, Anand S, Blankenberg S, Boehm BO, Clarke RJ, Collins R, Dedoussis G, Farrall M, Franks PW, Groop L, Hall AS, Hamsten A, Hengstenberg C, Hovingh GK, Ingelsson E, Kathiresan S, Kee F, König IR, Kooner J, Lehtimäki T, März W, McPherson R, Metspalu A, Nieminen MS, O'Donnell CJ, Palmer CN, Peters A, Perola M, Reilly MP, Ripatti S, Roberts R, Salomaa V, Shah SH, Schreiber S, Siegbahn A, Thorsteinsdottir U, Veronesi G, Wareham N, Willer CJ, Zalloua PA, Erdmann J, Deloukas P, Watkins H, Schunkert H, Danesh J, Thompson JR, Samani NJ; CARDIoGRAM+C4D Consortium.  Genetically determined height and coronary artery disease. N Engl J Med. 2015;372:1608-18. 

Ghosh S, Vivar J, Nelson C, Willenborg C, Segre A, Makinen VP, Nikpay M, Erdmann J, Blankenberg S, O'Donnell C, März W, Laaksonen R, Stewart A, Epstein S, Shah S, Granger C, Hazen S, Kathiresan S, Reilly M, Yang X, Quertermous T, Samani N, Schunkert H, Assimes T, McPherson R. Systems Genetics Analysis of GWAS reveals Novel Associations between Key Biological Processes and Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2015;35:1712-22.

Turner AW, McPherson R. PHACTR1: Functional clues linking a genome-wide association locus to coronary artery disease. Arterioscler Thromb Vasc Biol. 2015;35:1293-95.

Jansen H, Loley C, Lieb W, Pencina MJ, Nelson CP, Kathiresan S, Peloso GM, Voight BF, Reilly MP, Assimes TL, Boerwinkle E, Hengstenberg C, Laaksonen R, McPherson R, Roberts R, Thorsteinsdottir U, Peters A, Gieger C, Rawal R, Thompson JR, König IR; CARDIoGRAM consortium, Vasan RS, Erdmann J, Samani NJ, Schunkert H. Genetic variants primarily associated with type 2 diabetes are related to coronary artery disease risk. Atherosclerosis. 2015;241:419-426.

Huan T, Rong J, Tanriverdi K, Meng Q, Bhattacharya A, McManus DD, Joehanes R, Assimes TL,McPherson R, Samani NJ, Erdmann J, Schunkert H, Courchesne P, Munson PJ, Johnson AD, O'Donnell CJ, Zhang B, Larson MG, Freedman JE, Levy D, Yang X. Dissecting the Roles of MicroRNAs in Coronary Heart Disease via Integrative Genomic Analyses. Arterioscler Thromb Vasc Biol. 2015 Feb 5. pii: ATVBAHA.114.305176. [Epub ahead of print]

Cole CB, Nikpay M, McPherson R. Gene-environment interaction in dyslipidemia. Curr Opin Lipidol2015;26:133-8.

McPherson R. Obesity and ischemic heart disease: defining the link.  Circ Res. 2015;116:570-1. 



Liu DJ, Peloso GM, Zhan X, Holmen O, Zawitowski M, Feng S, Nikpay M, Auer PL, Goel A, Zhang H,  Peters R, Farrall M, Orho-Melander M,  Kooperberg C,  McPherson R, Watkins H, Melander O, Willer CJ,  Hveem K, Kathiresan S, Abecasis GR.  Meta-analysis of gene level association tests. Nature Genetics 2014;46:200-4.

Peloso GM, Auer PL, Bis JC, Voorman A, Morrison AC, Stitziel NO, Brody JA, Khetarpal SA, Crosby JR, Fornage M, Isaacs A, Jakobsdottir J, Feitosa MF, Davies G, Huffman JE, Manichaikul A, Davis B, Lohman K, Joon AY, Smith AV, Grove ML, Zanoni P, Redon V, Demissie S, Lawson K, Peters U, Carlson C, Jackson RD, Ryckman KK, Mackey RH, Robinson JG, Siscovick DS, Schreiner PJ, Mychaleckyj JC, Pankow JS, Hofman A, Uitterlinden AG, Harris TB, Taylor KD, Stafford JM, Reynolds LM, Marioni RE, Dehghan A, Franco OH, Patel AP, Lu Y, Hindy G, Gottesman O, Bottinger EP, Melander O, Orho-Melander M, Loos RJ, Duga S, Merlini PA, Farrall M, Goel A, Asselta R, Girelli D, Martinelli N, Shah SH, Kraus WE, Li M, Rader DJ, Reilly MP, McPherson R, Watkins H, Ardissino D; NHLBI GO Exome Sequencing Project, Zhang Q, Wang J, Tsai MY, Taylor HA, Correa A, Griswold ME, Lange LA, Starr JM, Rudan I, Eiriksdottir G, Launer LJ, Ordovas JM, Levy D, Chen YD, Reiner AP, Hayward C, Polasek O, Deary IJ, Borecki IB, Liu Y, Gudnason V, Wilson JG, van Duijn CM, Kooperberg C, Rich SS, Psaty BM, Rotter JI, O'Donnell CJ, Rice K, Boerwinkle E, Kathiresan S, Cupples LA. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary artery diease in 56,000 whites and blacks. Am J Hum Genet. 2014; 94:223-32.

Almontashiri NA, Vilmundarson RO, Ghasemzadeh N, Dandona S, Roberts R, Quyyumi AA, Chen HH, Stewart AF. Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies. PLoS One 2014;9:e106294.

Almontashiri NA, Chen HH, Mailloux RJ, Tatsuta T, Teng AC, Mahmoud AB, Ho T, Stewart NA, Rippstein P, Harper ME, Roberts R, Willenborg C, Erdmann J; CARDIoGRAM Consortium, Pastore A, McBride HM, Langer T, Stewart AF. SPG7 variant escapes phosphorylation-regulated processing by AFG3L2, elevates mitochondrial ROS, and is associated with multiple clinical phenotypes. Cell Rep. 2014;7:834-47

Lim, E. T., Wurtz, P., Havulinna, A. S., Palta, P., Tukiainen, T., Rehnstrom, K., Esko, T., Magi, R., Inouye, M., Lappalainen, T., Chan, Y., Salem, R. M., Lek, M., Flannick, J., Sim, X., Manning, A., Ladenvall, C., Bumpstead, S., Hamalainen, E., Aalto, K., Maksimow, M., Salmi, M., Blankenberg, S., Ardissino, D., Shah, S., Horne, B., McPherson, R., Hovingh, G. K., Reilly, M. P., Watkins, H., Goel, A., Farrall, M., Girelli, D., Reiner, A. P., Stitziel, N. O., Kathiresan, S., Gabriel, S., Barrett, J. C., Lehtimaki, T., Laakso, M., Groop, L., Kaprio, J., Perola, M., McCarthy, M. I., Boehnke, M., Altshuler, D. M., Lindgren, C. M., Hirschhorn, J. N., Metspalu, A., Freimer, N. B., Zeller, T., Jalkanen, S., Koskinen, S., Raitakari, O., Durbin, R., MacArthur, D. G., Salomaa, V., Ripatti, S., Daly, M. J., Palotie, A., & for the Sequencing Initiative Suomi (SISu) Project.  Distribution and medical impact of loss-of-function variants in the Finnish founder population. PLoS Genetics, 2014;10:e1004494. 

Mäkinen VP, Civelek M, Meng Q, Zhang B, Zhu J…Lusis AJ, Samani NJ, Schunkert H, Quertermous T, McPherson R, Yang X, AssimesTL. Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease. PLoS Genetics 2014;10:e1004502.

Crosby J, Peloso GM, Auer PL, Crosslin DR, Stitziel NO, Lange LA, Lu Y, Tang ZZ, Zhang H, Hindy G, Masca N, Stirrups K, Kanoni S, Do R, Jun G, Hu Y, Kang HM, Xue C, Goel A, Farrall M, Duga S, Merlini PA, Asselta R, Girelli D, Olivieri O, Martinelli N, Yin W, Reilly D, Speliotes E, Fox CS, Hveem K, Holmen OL, Nikpay M, Farlow DN, Assimes TL, Franceschini N, Robinson J, North KE, Martin LW, DePristo M, Gupta N, Escher SA, Jansson JH, Van Zuydam N, Palmer CN, Wareham N, Koch W, Meitinger T, Peters A, Lieb W, Erbel R, Konig IR, Kruppa J, Degenhardt F, Gottesman O, Bottinger EP, O'Donnell CJ, Psaty BM, Ballantyne CM, Abecasis G, Ordovas JM, Melander O, Watkins H, Orho-Melander M, Ardissino D, Loos RJ, McPherson R, Willer CJ, Erdmann J, Hall AS, Samani NJ, Deloukas P, Schunkert H, Wilson JG, Kooperberg C, Rich SS, Tracy RP, Lin DY, Altshuler D, Gabriel S, Nickerson DA, Jarvik GP, Cupples LA, Reiner AP, Boerwinkle E, Kathiresan S,  TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute, Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease. N Engl J Med 2014; 371:22-31.

Schick UM, Auer PL, Bis JC, Lin H, Wei P, Pankratz N, Lange LA, Brody J, Stitziel NO, Kim DS, Carlson CS, Fornage M, Haessler J, Hsu L, Jackson RD, Kooperberg C, Leal SM, Psaty BM, Boerwinkle E, Tracy R, Ardissino D, Shah S, Willer C, Loos R, Melander O, McPherson R, Hovingh K, Reilly M, Watkins H, Girelli D, Fontanillas P, Chasman DI, Gabriel SB, Gibbs R, Nickerson DA, Kathiresan S, Peters U, Dupuis J, Wilson JG, Rich SS, Morrison AC, Benjamin EJ, Gross MD, Reiner AP; on Behalf of the Cohorts for Heart and Aging Research in Genomic Epidemiology and the National Heart, Lung, and Blood Institute GO Exome Sequencing Project.Association os 3exome sequences with C-reactive protein levels in greater than 9000 participants. Hum Mol Genet. 2014;24:559-71

Cole CB, Nikpay M, Lau P, Stewart AF, Davies RW, Wells GA, Dent R, McPherson R. Adiposity significantly modifies genetic risk for dyslipidemia.  J Lipid Res.  2014;55:2416-22.

Stitziel NO, Won HH, Morrison AC, .…. Roden DM, Palmer C, Deloukas P, Lin DH, Tang ZZ, Erdmann J, Schunkert S, Danesh J, Marrugat S, Elosua R, Ardissino D, McPherson R, Watkins H, Reiner P, Wilson JG, Altshuler D, Gibbs RA, Lander ES, Boerwinkle E, Gabriel S, Kathiresan S. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med 2014;371:2072-82.



Erdmann J, Stark K, Esslinger UB, Rumpf PM, Koesling D, de Wit C, Kaiser FJ, Braunholz D, Medack A, Fischer M, Zimmermann ME, Tennstedt S, Graf E, Eck S, Aherrahrou Z, Nahrstaedt J, Willenborg C, Bruse P, Brænne I, Nöthen MM, Hofmann P, Braund PS, Mergia E, Reinhard W, Burgdorf C, Schreiber S, Balmforth AJ, Hall AS, Bertram L, Steinhagen-Thiessen E, Li SC, März W, Reilly M, Kathiresan S, McPherson R, Walter U, Cardiogram, Ott J, Samani NJ, Strom TM, Meitinger T, Hengstenberg C, Schunkert H. Dysfunctional nitric oxide signalling increases risk of myocardial infarction.  Nature 2013;504:432-436.

Fan M, Dandona S, McPherson R, Allayee H, Hazen SL, Wells GA, Roberts R, Stewart AF. Two Chromosome 9p21 Haplotype Blocks Distinguish Between Coronary Artery Disease and Myocardial Infarction Risk. Circ Cardiovasc Genet. 2013;6:372-80.

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McPherson R. Chromosome 9p21 and coronary artery disease. N Engl J Med 2010:362:1736-8 (invited commentary). 

Dandona S, Stewart AFR, Chen L, Williams K, So D, O’Brien E, Glover C, LeMay M, Vo L, Wang YQ, Labinaz M. Wells GA, McPherson R, Roberts R.  Gene dosage of the common variant 9p21 predicts severity of coronary artery disease.  J Am Coll Cardiol 2010;56:479-486. 



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Stewart AFR, Dandona S, Assogba O, Belanger M, Ewart G, LaRose R, Doelle H, Chen L, Williams K, Wells GA, McPherson R, Roberts R. Kinesin Family Member 6 variant Trp719Arg does not associate with coronary artery disease in the Ottawa Heart Genomics Study.  J Am Coll Cardiol  2009;53:1471-2. 



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