Centre canadien de génétique cardiovasculaire Ruddy

Le Centre canadien de génétique cardiovasculaire Ruddy, qui se consacre exclusivement à la recherche cardiovasculaire et à la prise en charge clinique des maladies héréditaires du cœur et des vaisseaux, est le premier centre complet de son genre au Canada.

Depuis la découverte en 2007 du locus (ou emplacement sur un chromosome) 9p21 qui prédispose à la maladie du cœur, nous avons, en collaboration avec divers groupes aux quatre coins du monde, identifié plus de 55 autres facteurs génétiques similaires qui ont un effet majeur sur le risque de maladie cardiaque.

Le Centre abrite par ailleurs les installations centrales d’analyse génétique, qui offrent des services de génotypage, de l’équipement spécialisé et de l’expertise technique aux chercheurs de l’Institut de cardiologie de l’Université d’Ottawa, à d’autres chercheurs dans le monde et aux services de génétique statistique.

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Publications

2016

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.

 

2015

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 RRayner 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 RStewart 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. 

 

2014

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 disease 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., Lehtimäki 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.

 

2013

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.

CARDIoGRAMplusC4D Consortium, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA, Stirrups K, König IR, Cazier JB, Johansson A, Hall AS, Lee JY, Willer CJ, Chambers JC, Esko T, Folkersen L, Goel A, Grundberg E, Havulinna AS, Ho WK, Hopewell JC, Eriksson N, Kleber ME, Kristiansson K, Lundmark P, Lyytikäinen LP, Rafelt S, Shungin D, Strawbridge RJ, Thorleifsson G, Tikkanen E, Van Zuydam N, Voight BF, Waite LL, Zhang W, Ziegler A, Absher D, Altshuler D, Balmforth AJ, Barroso I, Braund PS, Burgdorf C, Claudi-Boehm S, Cox D, Dimitriou M, Do R; DIAGRAM Consortium; CARDIOGENICS Consortium, Doney AS, El Mokhtari N, Eriksson P, Fischer K, Fontanillas P, Franco-Cereceda A, Gigante B, Groop L, Gustafsson S, Hager J, Hallmans G, Han BG, Hunt SE, Kang HM, Illig T, Kessler T, Knowles JW, Kolovou G, Kuusisto J, Langenberg C, Langford C, Leander K, Lokki ML, Lundmark A, McCarthy MI, Meisinger C, Melander O, Mihailov E, Maouche S, Morris AD, Müller-Nurasyid M; MuTHER Consortium, Nikus K, Peden JF, Rayner NW, Rasheed A, Rosinger S, Rubin D, Rumpf MP, Schäfer A, Sivananthan M, Song C, Stewart AF, Tan ST, Thorgeirsson G, van der Schoot CE, Wagner  PJ; Wellcome Trust Case Control Consortium, Wells GA, Wild PS, Yang TP, Amouyel P, Arveiler D, Basart H, Boehnke M, Boerwinkle E, Brambilla P, Cambien F, Cupples AL, de Faire U, Dehghan A, Diemert P, Epstein SE, Evans A, Ferrario MM, Ferrières J, Gauguier D, Go AS, Goodall AH, Gudnason V, Hazen SL, Holm H, Iribarren C, Jang Y, Kähönen M, Kee F, Kim HS, Klopp N, Koenig W, Kratzer W, Kuulasmaa K, Laakso M, Laaksonen R, Lee JY, Lind L, Ouwehand WH, Parish S, Park JE, Pedersen NL, Peters A, Quertermous T, Rader DJ, Salomaa V, Schadt E, Shah SH, Sinisalo J, Stark K, Stefansson K, Trégouët DA, Virtamo J, Wallentin L, Wareham N, Zimmermann ME, Nieminen MS, Hengstenberg C, Sandhu MS, Pastinen T, Syvänen AC, Hovingh GK, Dedoussis G, Franks PW, Lehtimäki T, Metspalu A, Zalloua PA, Siegbahn A, Schreiber S, Ripatti S, Blankenberg SS, Perola M, Clarke R, Boehm BO, O'Donnell C, Reilly MP, März W, Collins R, Kathiresan S, Hamsten A, Kooner JS, Thorsteinsdottir U, Danesh J, Palmer CN, Roberts R, Watkins H, Schunkert H, Samani NJ. Large scale association analysis identifies new risk loci for coronary artery disease.  Nat Genet. 2013;45:25-33.

 

2012

Davies RW,  Wells GA, Stewart AFR, Erdmann J, Shah SH, Ferguson JF, Hall AS, Anand SS, Burnett MS, Epstein SE, Dandona S, Chen L, Nahrstaedt J, Loley C, König IR, Kraus WE, Granger CB, Engert JC, Hengstenberg C, Wichmann HE, Schreiber S, Tang WHW, Ellis SG, Rader DJ, Hazen SL, Reilly MP, Samani NJ, Schunkert H, Roberts R, McPherson R.  A genome wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex. Circulation – Cardiovascular Genetics 2012;5:217-225

Grallert H, Dupuis J, Bis JC, Dehghan A, Barbalic M, Baumert J, Lu C, Smith NL, Uitterlinden AG, Roberts R, Khuseyinova N, Schnabel RB, Rice KM, Rivadeneira F, Hoogeveen RC, Fontes JD, Meisinger C, Keaney JF Jr, Lemaitre R, Aulchenko YS, Vasan RS, Ellis S, Hazen SL, van Duijn CM, Nelson JJ, März W, Schunkert H, McPherson R, Stirnadel-Farrant HA, Psaty BM, Gieger C, Siscovick D, Hofman A, Illig T, Cushman M, Yamamoto JF, Rotter JI, Larson MG, Stewart AF, Boerwinkle E, Witteman JC, Tracy RP, Koenig W, Benjamin EJ, Ballantyne CM. Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies.   Eur Heart J. 2012;33:238-251.

 

2011

Schunkert H, König IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, Absher D, Aherrahrou Z, Allayee H, Altshuler D, Anand SS, Andersen K, Anderson JL, Ardissino D, Ball SG, Balmforth AJ, Barnes TA, Becker DM, Becker LC, Berger K, Bis JC, Boekholdt SM, Boerwinkle E, Braund PS, Brown MJ, Burnett MS, Buysschaert I; Cardiogenics, Carlquist JF, Chen L, Cichon S, Codd V, Davies RW, Dedoussis G, Dehghan A, Demissie S, Devaney JM, Diemert P, Do R, Doering A, Eifert S, Mokhtari NE, Ellis SG, Elosua R, Engert JC, Epstein SE, de Faire U, Fischer M, Folsom AR, Freyer J, Gigante B, Girelli D, Gretarsdottir S, Gudnason V, Gulcher JR, Halperin E, Hammond N, Hazen SL, Hofman A, Horne BD, Illig T, Iribarren C, Jones GT, Jukema JW, Kaiser MA, Kaplan LM, Kastelein JJ, Khaw KT, Knowles JW, Kolovou G, Kong A, Laaksonen R, Lambrechts D, Leander K, Lettre G, Li M, Lieb W, Loley C, Lotery AJ, Mannucci PM, Maouche S, Martinelli N, McKeown PP, Meisinger C, Meitinger T, Melander O, Merlini PA, Mooser V, Morgan T, Mühleisen TW, Muhlestein JB, Münzel T, Musunuru K, Nahrstaedt J, Nelson CP, Nöthen MM, Olivieri O, Patel RS, Patterson CC, Peters A, Peyvandi F, Qu L, Quyyumi AA, Rader DJ, Rallidis LS, Rice C, Rosendaal FR, Rubin D, Salomaa V, Sampietro ML, Sandhu MS, Schadt E, Schäfer A, Schillert A, Schreiber S, Schrezenmeir J, Schwartz SM, Siscovick DS, Sivananthan M, Sivapalaratnam S, Smith A, Smith TB, Snoep JD, Soranzo N, Spertus JA, Stark K, Stirrups K, Stoll M, Tang WH, Tennstedt S, Thorgeirsson G, Thorleifsson G, Tomaszewski M, Uitterlinden AG, van Rij AM, Voight BF, Wareham NJ, Wells GA, Wichmann HE, Wild PS, Willenborg C, Witteman JC, Wright BJ, Ye S, Zeller T, Ziegler A, Cambien F, Goodall AH, Cupples LA, Quertermous T, März W, Hengstenberg C, Blankenberg S, Ouwehand WH, Hall AS, Deloukas P, Thompson JR, Stefansson K, Roberts R, Thorsteinsdottir U, O'Donnell CJ, McPherson R, Erdmann J; the CARDIoGRAM Consortium, Samani NJ. (McPherson R as one of 10 equally contributing senior authors). Thirteen novel genetic loci affecting risk of coronary artery disease. Nature Genetics 2011; 43:333-338.

 

2010

Davies  RW,  Dandona S,  Stewart AFR,  Chen L,  Ellis SG,  Tang WHW, Hazen SL,   Roberts R, McPherson R,  Wells, GA.  Improved prediction of cardiovascular disease based on a panel of SNPs identified through genome wide association studies.  Circulation: Cardiovascular Genetics 2010;3:468-74. 

Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O'Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PK, Lucas G, Luben R, Loos RJ, Lokki ML, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, König IR, Khaw KT, Kaprio J, Kaplan LM, Johansson A, Jarvelin MR, Cecile J W Janssens A, Ingelsson E, Igl W, Kees Hovingh G, Hottenga JJ, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Döring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJ, de Faire U, Crawford G, Collins FS, Chen YD, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Adair LS, Taylor HA Jr, Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteinsdottir U, Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010 Aug 5;466:707-13.

Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, Berrettini W, Knouff CW, Yuan X, Waeber G, Vollenweider P, Preisig M, Wareham NJ, Zhao JH, Loos RJ, Barroso I, Khaw KT, Grundy S, Barter P, Mahley R, Kesaniemi A, McPherson R, Vincent JB, Strauss J, Kennedy JL, Farmer A, McGuffin P, Day R, Matthews K, Bakke P, Gulsvik A, Lucae S, Ising M, Brueckl T, Horstmann S, Wichmann HE, Rawal R, Dahmen N, Lamina C, Polasek O, Zgaga L, Huffman J, Campbell S, Kooner J, Chambers JC, Burnett MS, Devaney JM, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Epstein S, Wilson JF, Wild SH, Campbell H, Vitart V, Reilly MP, Li M, Qu L, Wilensky R, Matthai W, Hakonarson HH, Rader DJ, Franke A, Wittig M, Schäfer A, Uda M, Terracciano A, Xiao X, Busonero F, Scheet P, Schlessinger D, Clair DS, Rujescu D, Abecasis GR, Grabe HJ, Teumer A, Völzke H, Petersmann A, John U, Rudan I, Hayward C, Wright AF, Kolcic I, Wright BJ, Thompson JR, Balmforth AJ, Hall AS, Samani NJ, Anderson CA, Ahmad T, Mathew CG, Parkes M, Satsangi J, Caulfield M, Munroe PB, Farrall M, Dominiczak A, Worthington J, Thomson W, Eyre S, Barton A; The Wellcome Trust Case Control Consortium, Mooser V, Francks C, Marchini J. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics  2010;42:436-40

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 RRoberts R.  Gene dosage of the common variant 9p21 predicts severity of coronary artery disease.  J Am Coll Cardiol 2010;56:479-486. 

 

2009

Soranzo N, Spector TD, Mangino M, Kühnel B, Rendon A, Teumer A, Willenborg C, Wright B, Chen L, Li M, Salo P, Voight BF, Burns P, Laskowski RA, Xue Y, Menzel S, Altshuler D, Bradley JR, Bumpstead S, Burnett MS, Devaney J, Döring A, Elosua R, Epstein SE, Erber W, Falchi M, Garner SF, Ghori MJ, Goodall AH, Gwilliam R, Hakonarson HH, Hall AS, Hammond N, Hengstenberg C, Illig T, König IR, Knouff CW, McPherson R, Melander O, Mooser V, Nauck M, Nieminen MS, O'Donnell CJ, Peltonen L, Potter SC, Prokisch H, Rader DJ, Rice CM, Roberts R, Salomaa V, Sambrook J, Schreiber S, Schunkert H, Schwartz SM, Serbanovic-Canic J, Sinisalo J, Siscovick DS, Stark K, Surakka I, Stephens J, Thompson JR, Völker U, Völzke H, Watkins NA, Wells GA, Wichmann HE, Van Heel DA, Tyler-Smith C, Thein SL, Kathiresan S, Perola M, Reilly MP, Stewart AF, Erdmann J, Samani NJ, Meisinger C, Greinacher A, Deloukas P, Ouwehand WH, Gieger C. A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.  Nat Genet. 2009;41:1182-90.  

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. 

 

2008

Sandhu MS, Waterworth DM, Debenham SL, Wheeler E, Papadakis K, Zhao JH, Song K, Yuan X, Johnson T, Ashford S, Inouye M, Luben R, Sims M, Hadley D, McArdle W, Barter P, Kesäniemi YA, Mahley RW, McPherson R, Grundy SM; Wellcome Trust Case Control Consortium, Bingham SA, Khaw KT, Loos RJ, Waeber G, Barroso I, Strachan DP, Deloukas P, Vollenweider P, Wareham NJ, Mooser V.  LDL-cholesterol concentrations: a genome-wide association study.  Lancet. 2008;371:483-91. 

 

2007

McPherson R, Pertsemlidides A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds D, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbc HH, Cohen JC.  A common allele on chromosome 9 associated with coronary heart disease. Science  2007;316:1488-91.  

Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Martin J, Hébert S, Doelle H, Ersoy B, Kryukov G, Schmidt S, Yosef N, Ruppin E,  Sharan R, Vaisse C, Sunyaev S, Dent R, Cohen J, McPherson R, Pennacchio LA. Medical sequencing at the extremes of human body mass.  Am J Human Genetics 2007;80:779-791  

Projets

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.