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6. Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data

Author

Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., Patel, R.S., Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., and Patel, R.S.

Abstract

Contains fulltext : 235380.pdf (Publisher’s version ) (Closed access), BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I(2)=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, card

Published
2020

8. Transoesophageal echocardiography in selecting patients for anticoagulation after ischaemic stroke or transient ischaemic attack. (Paper)

Author

Strandberg, M., Marttila, R.J., Helenius, H., and Hartiala, J.

Subjects
Stroke (Disease) -- Care and treatment, Anticoagulants (Medicine) -- Dosage and administration, Transesophageal echocardiography, Health, Psychology and mental health, Care and treatment, Dosage and administration
Abstract

Objectives: To investigate prospectively the role of transoesophageal echocardiography (TEE) in selecting patients for anticoagulation in an unselected stroke population. Methods: Transthoracic echocardiography (TTE) and TEE were done in all [...]

Published
2002

15. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events A GENIUS-CHD Study of Individual Participant Data

Author

Patel, R.S., Schmidt, A.F., Tragante, V., McCubrey, R.O., Holmes, M.V., Howe, L.J., Direk, K., Akerblom, A., Leander, K., Virani, S.S., Kaminski, K.A., Muehlschlegel, J.D., Dube, M.P., Allayee, H., Almgren, P., Alver, M., Baranova, E.V., Behlouli, H., Boeckx, B., Braund, P.S., Breitling, L.P., Delgado, G., Duarte, N.E., Dufresne, L., Eriksson, N., Foco, L., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Hubacek, J.A., Kleber, M., Kofink, D., Kuukasjarvi, P., Lee, V.V., Leiherer, A., Lenzini, P.A., Levin, D., Lyytikainen, L.P., Martinelli, N., Mons, U., Nelson, C.P., Nikus, K., Pilbrow, A.P., Ploski, R., Sun, Y.V., Tanck, M.W.T., Tang, W.H.W., Trompet, S., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Anselmi, C.V., Vlachopoulou, E., Boerwinkle, E., Briguori, C., Carlquist, J.F., Carruthers, K.F., Casu, G., Deanfield, J., Deloukas, P., Dudbridge, F., Fitzpatrick, N., Gigante, B., James, S., Lokki, M.L., Lotufo, P.A., Marziliano, N., Mordi, I.R., Muhlestein, J.B., Cheh, C.N., Pitha, J., Saely, C.H., Samman-Tahhan, A., Sandesara, P.B., Teren, A., Timmis, A., Werf, F. van de, Wauters, E., Wilde, A.A.M., Ford, I., Stott, D.J., Algra, A., Andreassi, M.G., Ardissino, D., Arsenault, B.J., Ballantyne, C.M., Bergmeijer, T.O., Bezzina, C.R., Body, S.C., Bogaty, P., Borst, G.J. de, Brenner, H., Burkhardt, R., Carpeggiani, C., Condorelli, G., Cooper-DeHoff, R.M., Cresci, S., Faire, U. de, Doughty, R.N., Drexel, H., Engert, J.C., Fox, K.A.A., Girelli, D., Hagstrom, E., Hazen, S.L., Held, C., Hemingway, H., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Jong, P.A. de, Jukema, J.W., Kaczor, M.P., Kahonen, M., Kettner, J., Kiliszek, M., Klungel, O.H., Lagerqvist, B., Lambrechts, D., Laurikka, J.O., Lehtimaki, T., Lindholm, D., Mahmoodi, B.K., Maitland-van der Zee, A.H., McPherson, R., Melander, O., Metspalu, A., Pepinski, W., Olivieri, O., Opolski, G., Palmer, C.N., Pasterkamp, G., Pepine, C.J., Pereira, A.C., Note, L., Quyyumi, A.A., Richards, A.M., Sanak, M., Scholz, M., Siegbahn, A., Sinisalo, J., Smith, J.G., Spertus, J.A., Stewart, A.F.R., Szczeklik, W., Szpakowicz, A., Berg, J.M. ten, Thanassoulis, G., Thieiy, J., Graaf, Y. van der, Visseren, F.L.J., Waltenberger, J., Harst, P. van der, Tardif, J.C., Sattar, N., Lang, C.C., Pare, G., Brophy, J.M., Anderson, J.L., Marz, W., Wallentin, L., Cameron, V.A., Horne, B.D., Samani, N.J., Hingorani, A.D., Asselbergs, F.W., and CARDIo-GRAMPlusC4D Consortium

Subjects
myocardial infarction, risk factor, cardiovascular diseases, chromosome, genetic, variation, secondary prevention
Abstract

BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Published
2019

16. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events

Author

Patel, RS, Schmidt, AF, Tragante, V, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Muehlschlegel, JD, Dubé, M-P, Allayee, H, Almgren, P, Alver, M, Baranova, EV, Behlouli, H, Boeckx, B, Braund, PS, Breitling, LP, Delgado, G, Duarte, NE, Dufresne, L, Eriksson, N, Foco, L, Gijsberts, CM, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Sun, YV, Tanck, MWT, Tang, WHW, Trompet, S, Van Der Laan, SW, Van Setten, J, Vilmundarson, RO, Anselmi, C, Vlachopoulou, E, Boerwinkle, E, Briguori, C, Carlquist, JF, Carruthers, KF, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Fitzpatrick, N, Gigante, B, James, S, Lokki, M-L, Lotufo, PA, Marziliano, N, Mordi, IR, Muhlestein, JB, Newton-Cheh, C, Pitha, J, Saely, CH, Samman-Tahhan, A, Sandesara, PB, Teren, A, Timmis, A, Van De Werf, F, Wauters, E, Wilde, AAM, Ford, I, Stott, DJ, Algra, A, Andreassi, MG, Ardissino, D, Arsenault, BJ, Ballantyne, CM, Bergmeijer, TO, Bezzina, CR, Body, SC, Bogaty, P, De Borst, GJ, Brenner, H, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-Dehoff, RM, Cresci, S, De Faire, U, Doughty, RN, Drexel, H, Engert, JC, Fox, KAA, Girelli, D, Hagström, E, Hazen, SL, Held, C, Hemingway, H, Hoefer, IE, Hovingh, GK, Johnson, JA, De Jong, PA, Jukema, JW, Kaczor, MP, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, OH, Lagerqvist, B, Lambrechts, D, Laurikka, JO, Lehtimäki, T, Lindholm, D, Mahmoodi, BK, Der Zee, AH, McPherson, R, Melander, O, Metspalu, A, Pepinski, W, Olivieri, O, Opolski, G, Palmer, CN, Pasterkamp, G, Pepine, CJ, Pereira, AC, Pilote, L, Quyyumi, AA, Richards, AM, Sanak, M, Scholz, M, Siegbahn, A, Sinisalo, J, Smith, JG, Spertus, JA, Stewart, AFR, Szczeklik, W, Szpakowicz, A, Berg, JM, Thanassoulis, G, Thiery, J, Van Der Graaf, Y, Visseren, FLJ, Waltenberger, J, Van Der Harst, P, Tardif, J-C, Sattar, N, Lang, CC, Paré, G, Brophy, JM, Anderson, JL, März, W, Wallentin, L, Cameron, VA, Horne, BD, Samani, NJ, Hingorani, AD, and Asselbergs, FW

Subjects
Male, Myocardial Infarction, genetic risk factor, Coronary Artery Disease, Middle Aged, Article, chromosome 9p21, Gene Frequency, Risk Factors, Case-Control Studies, Odds Ratio, Humans, Female, Genetic Predisposition to Disease, cardiovascular diseases, Chromosomes, Human, Pair 9, secondary prevention
Abstract

Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Published
2019

17. Subsequent Event Risk in Individuals With Established Coronary Heart Disease

Author

Patel, R.S. (Riyaz), Tragante, V. (Vinicius), Schmidt, A.F. (Amand), McCubrey, R.O. (Raymond O.), Holmes, M.V. (Michael), Howe, L.J. (Laurence J.), Direk, K. (Kenan), Åkerblom, A. (Axel), Leander, K. (Karin), Virani, S.S. (Salim), Kaminski, K.A. (Karol A.), Muehlschlegel, J.D. (Jochen), Allayee, H. (Hooman), Almgren, P. (Peter), Alver, M. (Maris), Baranova, E.V. (Ekaterina V.), Behloui, H. (Hassan), Boeckx, B. (Bram), Braund, P.S. (Peter), Breitling, L.P. (Lutz), Delgado, G., Duarte, N.E. (Nubia E.), Dubé, G.P. (Gregory), Dufresne, L. (Line), Eriksson, N. (Niclas), Foco, L. (Luisa), Scholz, M. (Markus), Gijsberts, C.M. (Crystel M.), Glinge, C. (Charlotte), Gong, Y. (Yan), Hartiala, J. (Jaana), Heydarpour, M. (Mahyar), Hubacek, J.A. (Jaroslav A.), Kleber, M.E. (Marcus), Kofink, D. (Daniel), Kotti, S. (Salma), Kuukasjärvi, P. (Pekka), Lee, V.-V. (Vei-Vei), Leiherer, A. (Andreas), Lenzini, P.A. (Petra A.), Levin, D. (Daniel), Lyytikäinen, L.-P. (Leo-Pekka), Martinelli, N. (Nicola), Mons, U. (Ute), Nelson, C.P. (Christopher P.), Nikus, K. (Kjell), Pilbrow, A.P. (Anna P.), Ploski, R. (Rafal), Sun, Y.V. (Yan V.), Tanck, M.W.T. (Michael), Tang, W. (W.), Trompet, S. (Stella), van der Laan, S.W. (Sander W.), Setten, J. (Jessica) van, Vilmundarson, R.O. (Ragnar O.), Viviani Anselmi, C. (Chiara), Vlachopoulou, E. (Efthymia), Al Ali, L. (Lawien), Boerwinkle, E.A. (Eric), Briguori, C. (Carlo), Carlquist, J.F. (John), Carruthers, K.F. (Kathryn), Casu, G. (Gavino), Deanfield, J. (John), Deloukas, P. (Panos), Dudbridge, F. (Frank), Engstrøm, T. (Thomas), Fitzpatrick, N. (Natalie), Fox, K.M. (Kim), Gigante, B. (Bruna), James, S.K. (Stefan), Lokki, M.-L. (Marja-Liisa), Lotufo, P.A. (Paulo A.), Marziliano, N. (Nicola), Mordi, I.R. (Ify R.), Muhlestein, J.B. (Joseph), Newton-Cheh, C. (Christopher), Pitha, J. (Jan), Saely, C.H. (Christoph H.), Samman-Tahhan, A. (Ayman), Sandesara, P.B. (Pratik B.), Teren, A. (Andrej), Timmis, A. (Adam), Van de Werf, F. (Frans), Wilde, A.A.M. (Arthur), Ford, I. (Ian), Stott, D.J. (David. J.), Algra, A. (Ale), Andreassi, M.G. (Maria G.), Ardissino, D. (Diego), Arsenault, B.J. (Benoit J.), Ballantyne, C. (Christie), Bergmeijer, T.O. (Thomas O.), Bezzina, C.R. (Connie R.), Body, S.C. (Simon C.), Boersma, E.H. (Eric H.), Bogaty, P. (Peter), Bots, M.L. (Michiel), Brenner, H. (Hermann), Brugts, J.J. (Jasper), Burkhardt, R. (Ralph), Carpeggiani, C. (Clara), Condorelli, G. (Gianluigi), Cooper-Dehoff, R.M. (Rhonda), Cresci, S. (Sharon), Danchin, N. (Nicolas), Faire, U. (Ulf) de, Doughty, R.N. (Robert N.), Drexel, H. (Heinz), Engert, J.C. (James C.), Fox, K.A.A. (Keith), Girelli, D. (Domenico), Grobbee, D.E. (Diederick E.), Hagström, E. (Emil), Hazen, S.L. (Stanley), Held, C. (Claes), Hemingway, H., Hoefer, I.E. (Imo), Hovingh, G.K. (G Kees), Jabbari, R. (Reza), Johnson, J.A. (Jennifer ), Jukema, J.W. (Jan Wouter), Kaczor, M.P. (Marcin P.), Kähönen, M. (Mika), Kettner, J. (Jiri), Kiliszek, M. (Marek), Klungel, O.H. (Olaf), Lagerqvist, B. (Bo), Lambrechts, D. (Diether), Laurikka, J.O. (Jari O.), Lehtimäki, T. (Terho), Lindholm, D. (Daniel), Mahmoodi, B.K. (Bakhtawar K.), Maitland-van der Zee, A-H. (Anke-Hilse), McPherson, R. (Ruth), Melander, O. (Olle), Metspalu, A. (Andres), Niemcunowicz-Janica, A. (Anna), Olivieri, O. (Oliviero), Opolski, G. (Grzegorz), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Pepine, C.J. (Carl), Pereira, A. (A.), Pilote, L. (Louise), Erdmann, J. (Jeanette), Richards, A.M. (A Mark), Sanak, M. (Marek), Siegbahn, A. (Agneta), Simon, T. (Tabassome), Sinisalo, J. (Juha), Smith, J.G. (J Gustav), Schwartz, S.M. (Stephen), Stender, S. (Steen), Stewart, A.F. (Alexandre F.), Szczeklik, W. (Wojciech), Szpakowicz, A. (Anna), Tardif, J.-C. (Jean-Claude), Berg, J.M. (Jurrien) ten, Tfelt-Hansen, J. (Jacob), Thanassoulis, G. (George), Thiery, J.P. (Joachim), Torp-Pedersen, C. (Christian Tobias), Graaf, Y. (Yolanda) van der, Visseren, F.L.J. (Frank), Waltenberger, J. (Johannes), Weeke, P.E. (Peter E.), Harst, P. (Pim) van der, Lang, C.C. (Chim C.), Sattar, N. (Naveed), Cameron, V.A. (Vicky A.), Anderson, J.L. (Jeffrey), Brophy, J.M. (James M.), Pare, G. (Guillame), Horne, B.D. (Benjamin), Ye, S. (Shu), Wallentin, L. (Lars), Wauters, E. (Els), Samani, N.J. (Nilesh), Hingorani, A. (Aroon), Asselbergs, F.W. (Folkert), Patel, R.S. (Riyaz), Tragante, V. (Vinicius), Schmidt, A.F. (Amand), McCubrey, R.O. (Raymond O.), Holmes, M.V. (Michael), Howe, L.J. (Laurence J.), Direk, K. (Kenan), Åkerblom, A. (Axel), Leander, K. (Karin), Virani, S.S. (Salim), Kaminski, K.A. (Karol A.), Muehlschlegel, J.D. (Jochen), Allayee, H. (Hooman), Almgren, P. (Peter), Alver, M. (Maris), Baranova, E.V. (Ekaterina V.), Behloui, H. (Hassan), Boeckx, B. (Bram), Braund, P.S. (Peter), Breitling, L.P. (Lutz), Delgado, G., Duarte, N.E. (Nubia E.), Dubé, G.P. (Gregory), Dufresne, L. (Line), Eriksson, N. (Niclas), Foco, L. (Luisa), Scholz, M. (Markus), Gijsberts, C.M. (Crystel M.), Glinge, C. (Charlotte), Gong, Y. (Yan), Hartiala, J. (Jaana), Heydarpour, M. (Mahyar), Hubacek, J.A. (Jaroslav A.), Kleber, M.E. (Marcus), Kofink, D. (Daniel), Kotti, S. (Salma), Kuukasjärvi, P. (Pekka), Lee, V.-V. (Vei-Vei), Leiherer, A. (Andreas), Lenzini, P.A. (Petra A.), Levin, D. (Daniel), Lyytikäinen, L.-P. (Leo-Pekka), Martinelli, N. (Nicola), Mons, U. (Ute), Nelson, C.P. (Christopher P.), Nikus, K. (Kjell), Pilbrow, A.P. (Anna P.), Ploski, R. (Rafal), Sun, Y.V. (Yan V.), Tanck, M.W.T. (Michael), Tang, W. (W.), Trompet, S. (Stella), van der Laan, S.W. (Sander W.), Setten, J. (Jessica) van, Vilmundarson, R.O. (Ragnar O.), Viviani Anselmi, C. (Chiara), Vlachopoulou, E. (Efthymia), Al Ali, L. (Lawien), Boerwinkle, E.A. (Eric), Briguori, C. (Carlo), Carlquist, J.F. (John), Carruthers, K.F. (Kathryn), Casu, G. (Gavino), Deanfield, J. (John), Deloukas, P. (Panos), Dudbridge, F. (Frank), Engstrøm, T. (Thomas), Fitzpatrick, N. (Natalie), Fox, K.M. (Kim), Gigante, B. (Bruna), James, S.K. (Stefan), Lokki, M.-L. (Marja-Liisa), Lotufo, P.A. (Paulo A.), Marziliano, N. (Nicola), Mordi, I.R. (Ify R.), Muhlestein, J.B. (Joseph), Newton-Cheh, C. (Christopher), Pitha, J. (Jan), Saely, C.H. (Christoph H.), Samman-Tahhan, A. (Ayman), Sandesara, P.B. (Pratik B.), Teren, A. (Andrej), Timmis, A. (Adam), Van de Werf, F. (Frans), Wilde, A.A.M. (Arthur), Ford, I. (Ian), Stott, D.J. (David. J.), Algra, A. (Ale), Andreassi, M.G. (Maria G.), Ardissino, D. (Diego), Arsenault, B.J. (Benoit J.), Ballantyne, C. (Christie), Bergmeijer, T.O. (Thomas O.), Bezzina, C.R. (Connie R.), Body, S.C. (Simon C.), Boersma, E.H. (Eric H.), Bogaty, P. (Peter), Bots, M.L. (Michiel), Brenner, H. (Hermann), Brugts, J.J. (Jasper), Burkhardt, R. (Ralph), Carpeggiani, C. (Clara), Condorelli, G. (Gianluigi), Cooper-Dehoff, R.M. (Rhonda), Cresci, S. (Sharon), Danchin, N. (Nicolas), Faire, U. (Ulf) de, Doughty, R.N. (Robert N.), Drexel, H. (Heinz), Engert, J.C. (James C.), Fox, K.A.A. (Keith), Girelli, D. (Domenico), Grobbee, D.E. (Diederick E.), Hagström, E. (Emil), Hazen, S.L. (Stanley), Held, C. (Claes), Hemingway, H., Hoefer, I.E. (Imo), Hovingh, G.K. (G Kees), Jabbari, R. (Reza), Johnson, J.A. (Jennifer ), Jukema, J.W. (Jan Wouter), Kaczor, M.P. (Marcin P.), Kähönen, M. (Mika), Kettner, J. (Jiri), Kiliszek, M. (Marek), Klungel, O.H. (Olaf), Lagerqvist, B. (Bo), Lambrechts, D. (Diether), Laurikka, J.O. (Jari O.), Lehtimäki, T. (Terho), Lindholm, D. (Daniel), Mahmoodi, B.K. (Bakhtawar K.), Maitland-van der Zee, A-H. (Anke-Hilse), McPherson, R. (Ruth), Melander, O. (Olle), Metspalu, A. (Andres), Niemcunowicz-Janica, A. (Anna), Olivieri, O. (Oliviero), Opolski, G. (Grzegorz), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Pepine, C.J. (Carl), Pereira, A. (A.), Pilote, L. (Louise), Erdmann, J. (Jeanette), Richards, A.M. (A Mark), Sanak, M. (Marek), Siegbahn, A. (Agneta), Simon, T. (Tabassome), Sinisalo, J. (Juha), Smith, J.G. (J Gustav), Schwartz, S.M. (Stephen), Stender, S. (Steen), Stewart, A.F. (Alexandre F.), Szczeklik, W. (Wojciech), Szpakowicz, A. (Anna), Tardif, J.-C. (Jean-Claude), Berg, J.M. (Jurrien) ten, Tfelt-Hansen, J. (Jacob), Thanassoulis, G. (George), Thiery, J.P. (Joachim), Torp-Pedersen, C. (Christian Tobias), Graaf, Y. (Yolanda) van der, Visseren, F.L.J. (Frank), Waltenberger, J. (Johannes), Weeke, P.E. (Peter E.), Harst, P. (Pim) van der, Lang, C.C. (Chim C.), Sattar, N. (Naveed), Cameron, V.A. (Vicky A.), Anderson, J.L. (Jeffrey), Brophy, J.M. (James M.), Pare, G. (Guillame), Horne, B.D. (Benjamin), Ye, S. (Shu), Wallentin, L. (Lars), Wauters, E. (Els), Samani, N.J. (Nilesh), Hingorani, A. (Aroon), and Asselbergs, F.W. (Folkert)

Abstract

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants a

Published
2019
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18. Genetic determinants of circulating glycine levels and risk of coronary artery disease

Author

Jia, Q. (Qiong), Han, Y. (Yi), Huang, P. (Pin), Woodward, N. C. (Nicholas C.), Gukasyan, J. (Janet), Kettunen, J. (Johannes), Ala‐Korpela, M. (Mika), Anufrieva, O. (Olga), Wang, Q. (Qin), Perola, M. (Markus), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Järvelin, M. (Marjo‐Riitta), Boehnke, M. (Michael), Laakso, M. (Markku), Mohlke, K. L. (Karen L.), Fiehn, O. (Oliver), Wang, Z. (Zeneng), Tang, W. W. (W.H. Wilson), Hazen, S. L. (Stanley L.), Hartiala, J. A. (Jaana A.), Allayee, H. (Hooman), Jia, Q. (Qiong), Han, Y. (Yi), Huang, P. (Pin), Woodward, N. C. (Nicholas C.), Gukasyan, J. (Janet), Kettunen, J. (Johannes), Ala‐Korpela, M. (Mika), Anufrieva, O. (Olga), Wang, Q. (Qin), Perola, M. (Markus), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Järvelin, M. (Marjo‐Riitta), Boehnke, M. (Michael), Laakso, M. (Markku), Mohlke, K. L. (Karen L.), Fiehn, O. (Oliver), Wang, Z. (Zeneng), Tang, W. W. (W.H. Wilson), Hazen, S. L. (Stanley L.), Hartiala, J. A. (Jaana A.), and Allayee, H. (Hooman)

Abstract

Background: Recent studies have revealed sexually dimorphic associations between the carbamoyl‐phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease (CAD) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl‐phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results: We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta‐analysis of genome‐wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine‐associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism (ACADM,PHGDH,COX18‐ADAMTS3,PSPH,TRIB1,PTPRD, and ABO). Glycine‐raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD. However, these effects could not be attributed directly to glycine because of associations with other CAD‐related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity‐related traits. Conclusions: These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.

Published
2019

24. Comparative Genome-Wide Association Studies in Mice and Humans for Trimethylamine N -Oxide, a Proatherogenic Metabolite of Choline and <scp>l</scp> -Carnitine

Author

Hartiala, J., Bennett, B.J., Tang, W.H.W., Wang, Z., Stewart, A.F.R., Roberts, R., McPherson, R., CARDIoGRAM Consortium (Döring, A., Illig, T., Klopp, N., Meisinger, C., Meitinger, T., Peters, A., Wichmann, H.-E.), Lusis, A., Hazen, S.L., and Allayee, H.

Subjects
Male, Locus (genetics), Trimethylamine N-oxide, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, Choline, Methylamines, Mice, chemistry.chemical_compound, Carnitine, Animals, Humans, Atherosclerosis, Genetics, Cation Transport Proteins, Gene, Aged, Middle Aged, Solute carrier family, Chromosome 3, chemistry, Chromosomes, Human, Pair 1, Multigene Family, Expression quantitative trait loci, Oxygenases, Female, Cardiology and Cardiovascular Medicine, Genome-Wide Association Study
Abstract

Objective— Elevated levels of plasma trimethylamine N -oxide (TMAO), the product of gut microbiome and hepatic-mediated metabolism of dietary choline and l -carnitine, have recently been identified as a novel risk factor for the development of atherosclerosis in mice and humans. The goal of this study was to identify the genetic factors associated with plasma TMAO levels. Approach and Results— We used comparative genome-wide association study approaches to discover loci for plasma TMAO levels in mice and humans. A genome-wide association study in the hybrid mouse diversity panel identified a locus for TMAO levels on chromosome 3 ( P =2.37×10 −6 ) that colocalized with a highly significant ( P =1.07×10 −20 ) cis -expression quantitative trait locus for solute carrier family 30 member 7. This zinc transporter could thus represent 1 positional candidate gene responsible for the association signal at this locus in mice. A genome-wide association study for plasma TMAO levels in 1973 humans identified 2 loci with suggestive evidence of association ( P =3.0×10 −7 ) on chromosomes 1q23.3 and 2p12. However, genotyping of the lead variants at these loci in 1892 additional subjects failed to replicate their association with plasma TMAO levels. Conclusions— The results of these limited observational studies indicate that, at least in humans, genes play a marginal role in determining TMAO levels and that any genetic effects are relatively weak and complex. Variation in diet or the repertoire of gut microbiota may be more important determinants of plasma TMAO levels in mice and humans, which should be investigated in future studies.

Published
2014

26. Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: A collaborative meta-analysis

Author

Chan, K, Patel, R, Newcombe, P, Nelson, C, Qasim, A, Epstein, SE, Burnett, S, Vaccarino, V, Zafari, A, Shah, S, Anderson, J, Carlquist, J, Hartiala, J, Allayee, H, Hinohara, K, Lee, B, Erl, A, Ellis, K, Goel, A, Schaefer, A, El Mokhtari, N, Goldstein, B, Hlatky, M, Go, A, and Shen, G

Abstract

Objectives: This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD. Background: Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. Methods: We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects. Results: We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele. Conclusions: The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype. © 2013 American College of Cardiology Foundation.

Published
2016

27. A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site

Author

Nürnberg ST, Rendon A, Smethurst PA, Paul DS, Voss K, Thon JN, Lloyd Jones H, Sambrook JG, Tijssen MR, Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, Serbanovic Canic J, Elling U, Goodall AH, Labrune Y, Lopez LM, Mägi R, Meacham S, Okada Y, Sorice R, Teumer A, Zhang W, Ramirez Solis R, Bis JC, Ellinghaus D, Gögele M, Hottenga JJ, Langenberg C, Kovacs P, F. P, Shin SY, Esko T, Hartiala J, Kanoni S, Murgia F, Parsa A, Stephens J, van der Harst P, van der Schoot C, Allayee H, Attwood A, Balkau B, Bastardot F, Basu S, Baumeister SE, Biino G, Bomba L, Bonnefond A, Cambien F, Chambers JC, Cucca F, Davies G, de Geus EJ, de Boer RA, Döring A, Elliott P, Erdmann J, Feng W, Evans DM, Falchi M, Folsom AR, Frazer IH, Gibson QD, Glazer NL, Hammond C, Hartikainen AL, Heckbert SR, Hengstenberg C, Hersch M, Illig T, Loos RJ, Jolley J, Khaw KT, Kühnel B, Kyrtsonis MC, Lagou V, Lumley T, Mangino M, Maschio A, Mateo Leach I, McKnight B, Memari Y, Mitchell BD, Montgomery GW, Nöthlings U, Nakamura Y, Nauck M, Navis G, Nolte IM, Porteous DJ, Pouta A, Pramstaller PP, Pullat J, Ring SM, Rotter JI, Ruggiero D, Ruokonen A, Sala C, Samani NJ, Sambrook J, Schlessinger D, Schreiber S, Schunkert H, Scott J, Smith NL, Snieder H, Starr JM, Stumvoll M, Takahashi A, Taylor K, Tenesa A, Thein SL, Tönjes A, Uda M, Ulivi S, Wichmann HE, Yang TP, van Veldhuisen DJ, Visscher PM, Völker U, Wiggins KL, Willemsen G, Zhao JH, Zitting P, Bradley JR, Dedoussis GV, Hazen SL, Metspalu A, Pirastu M, Shuldiner AR, van Pelt L, Zwaginga JJ, Boomsma DI, Deary IJ, Franke A, Froguel P, Ganesh SK, Jarvelin MR, Martin NG, Meisinger C, Psaty BM, Spector TD, Wareham NJ, Akkerman JW, Ciullo M, Deloukas P, Greinacher A, Jupe S, Kamatani N, Khadake J, Kooner JS, Penninger J, Prokopenko I, Stemple D, Toniolo D, Wernisch L, Sanna S, Hicks AA, Ferreira MA, Italiano JE Jr, Gottgens B, Soranzo N, Ouwehand WH, PIRASTU, Nicola, D'ADAMO, ADAMO PIO, GASPARINI, PAOLO, Nürnberg, St, Rendon, A, Smethurst, Pa, Paul, D, Voss, K, Thon, Jn, Lloyd Jones, H, Sambrook, Jg, Tijssen, Mr, Gieger, C, Radhakrishnan, A, Cvejic, A, Tang, W, Porcu, E, Pistis, G, Serbanovic Canic, J, Elling, U, Goodall, Ah, Labrune, Y, Lopez, Lm, Mägi, R, Meacham, S, Okada, Y, Pirastu, Nicola, Sorice, R, Teumer, A, Zhang, W, Ramirez Solis, R, Bis, Jc, Ellinghaus, D, Gögele, M, Hottenga, Jj, Langenberg, C, Kovacs, P, F., P, Shin, Sy, Esko, T, Hartiala, J, Kanoni, S, Murgia, F, Parsa, A, Stephens, J, van der Harst, P, van der Schoot, C, Allayee, H, Attwood, A, Balkau, B, Bastardot, F, Basu, S, Baumeister, Se, Biino, G, Bomba, L, Bonnefond, A, Cambien, F, Chambers, Jc, Cucca, F, D'Adamo, ADAMO PIO, Davies, G, de Geus, Ej, de Boer, Ra, Döring, A, Elliott, P, Erdmann, J, Feng, W, Evans, Dm, Falchi, M, Folsom, Ar, Frazer, Ih, Gibson, Qd, Glazer, Nl, Hammond, C, Hartikainen, Al, Heckbert, Sr, Hengstenberg, C, Hersch, M, Illig, T, Loos, Rj, Jolley, J, Khaw, Kt, Kühnel, B, Kyrtsonis, Mc, Lagou, V, Lumley, T, Mangino, M, Maschio, A, Mateo Leach, I, Mcknight, B, Memari, Y, Mitchell, Bd, Montgomery, Gw, Nöthlings, U, Nakamura, Y, Nauck, M, Navis, G, Nolte, Im, Porteous, Dj, Pouta, A, Pramstaller, Pp, Pullat, J, Ring, Sm, Rotter, Ji, Ruggiero, D, Ruokonen, A, Sala, C, Samani, Nj, Sambrook, J, Schlessinger, D, Schreiber, S, Schunkert, H, Scott, J, Smith, Nl, Snieder, H, Starr, Jm, Stumvoll, M, Takahashi, A, Taylor, K, Tenesa, A, Thein, Sl, Tönjes, A, Uda, M, Ulivi, S, Wichmann, He, Yang, Tp, van Veldhuisen, Dj, Visscher, Pm, Völker, U, Wiggins, Kl, Willemsen, G, Zhao, Jh, Zitting, P, Bradley, Jr, Dedoussis, Gv, Gasparini, Paolo, Hazen, Sl, Metspalu, A, Pirastu, M, Shuldiner, Ar, van Pelt, L, Zwaginga, Jj, Boomsma, Di, Deary, Ij, Franke, A, Froguel, P, Ganesh, Sk, Jarvelin, Mr, Martin, Ng, Meisinger, C, Psaty, Bm, Spector, Td, Wareham, Nj, Akkerman, Jw, Ciullo, M, Deloukas, P, Greinacher, A, Jupe, S, Kamatani, N, Khadake, J, Kooner, J, Penninger, J, Prokopenko, I, Stemple, D, Toniolo, D, Wernisch, L, Sanna, S, Hicks, Aa, Ferreira, Ma, Italiano JE, Jr, Gottgens, B, Soranzo, N, Ouwehand, Wh, Biological Psychology, and EMGO+ - Mental Health

Subjects
Netherlands Twin Register (NTR), Transcription, Genetic, Gene Expression, Biochemistry, megakaryocyte, Mice, DNM3 promoter, Transcription (biology), GWAS, Platelet, Thrombopoiesis, Myeloid Ecotropic Viral Integration Site 1 Protein, Promoter Regions, Genetic, Cells, Cultured, Reverse Transcriptase Polymerase Chain Reaction, Hematology, Neoplasm Proteins, Haematopoiesis, Transcription Initiation Site, Megakaryocytes, platelet volume, DNM3, megakaryocytes, MEIS1, Blood Platelets, Chromatin Immunoprecipitation, Immunology, Biology, Polymorphism, Single Nucleotide, MEIS1 binding site, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Animals, Humans, Cell Lineage, Binding site, Gene, Transcription factor, Homeodomain Proteins, Binding Sites, Genome, Human, Platelet Count, Hydrazones, Genetic Variation, Cell Biology, Sequence Analysis, DNA, Platelets and Thrombopoiesis, Molecular biology, Dynamin III
Abstract

We recently identified 68 genomic loci where common sequence variants are associated with platelet count and volume. Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly controlled by transcription factors. The homeobox transcription factor MEIS1 is uniquely transcribed in megakaryocytes and not in the other lineage-committed blood cells. By ChIP-seq, we show that 5 of the 68 loci pinpoint a MEIS1 binding event within a group of 252 MK-overexpressed genes. In one such locus in DNM3, regulating platelet volume, the MEIS1 binding site falls within a region acting as an alternative promoter that is solely used in megakaryocytes, where allelic variation dictates different levels of a shorter transcript. The importance of dynamin activity to the latter stages of thrombopoiesis was confirmed by the observation that the inhibitor Dynasore reduced murine proplatelet for-mation in vitro.

Published
2013

29. A Genome-wide Scan Identifies a Genetic Locus for Migraine with Aura

Author

Wessman, M., Kallela, M., Oswell, G., Kaunisto, M., Hartiala, J., Broas, P., Hamalainen, E., Marttila, P., Hiekkalinna, T., Joslyn, G. Papp, J., Leal, S.M., Cantor, R., Sobel, E., Ott, J., Havanka, H., Farkkila, M., Peltonen, L., and Palotie, A.

Subjects
Genetic disorders -- Research, Migraine -- Genetic aspects, Aura, Biological sciences
Published
2001

30. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies

Author

Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ, Qasim AN, DerOhannessian SL, Qu L, Cappola TP, Chen Z, Matthai W, Hakonarson HH, Wilensky R, Kent KM, Lindsay JM, Pichard AD, Satler L, Waksman R, Knoupf CW, Walker MC, Waterworth DM, Mosser V, Braund PS, Wright B, Balmforth AJ, Ball SG, Chen L, Wells GA, McPherson R, Lackner K, Munzel TF, Schillert A, Schnabel R, Zeller T, Ziegler A, Absher D, Hlatky MA, Iribaren C, Knowles JW, Linsel Nitschke P, König IR, Hengstenberg C, Nahrstaedt J, Peters A, Schreiber S, Wichmann E, Willenborg C, Su S, Bouzyk M, Vaccarino V, Zafari AM, Carlquist JF, Muhlestein JB, Olivieri O, Barnard J, Hartiala J, Tang WH, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Dixon RJ, Mangino M, Stevens S, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop M, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, 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Subjects
Adult, Male, medicine.medical_specialty, Linkage disequilibrium, ABO, ADAMTS7 Protein, ADAMTS7, Genome-wide association study, Coronary Angiography, Polymorphism, Single Nucleotide, Linkage Disequilibrium, ABO Blood-Group System, Coronary artery disease, Gene Frequency, ABO blood group system, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Myocardial infarction, Genetic risk factor, genetic locus, Coronary atherosclerosis, Aged, business.industry, coronary atherosclerosis, General Medicine, Middle Aged, medicine.disease, ADAM Proteins, myocardial infarction, Genetic Loci, Cardiology, Myocardial infarction complications, Female, business, coronary artery disease, Genome-Wide Association Study
Abstract

BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. METHODS: We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). FINDINGS: In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. INTERPRETATION: Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. FUNDING: The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.

Published
2011

31. Comparative Genome-Wide Association Studies in Mice and Humans for Trimethylamine N-Oxide, a Proatherogenic Metabolite of Choline and L-Carnitine

Author

Tang, W. H. W., Allayee, H., Lusis, A. J., Roberts, R., McPherson, R., Wang, Z., Bennett, B. J., Stewart, A. F. R., Hartiala, J., and Hazen, S. L.

Abstract

Elevated levels of plasma trimethyl amine N-oxide (TMAO), the product of gut microbiome and hepatic-mediated metabolism of dietary choline and L-carnitine, have recently been identified as a novel risk factor for the development of atherosclerosis in mice and humans. The goals of this study were to identify the genetic factors associated with plasma TMAO levels.

Published
2014
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33. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

Author

Kato, N. (Norihiro), Loh, M. (Marie), Takeuchi, F. (Fumihiko), Verweij, N. (Niek), Wang, X. (Xu), Zhang, W. (Weihua), NKelly, T. (Tanika), Saleheen, D., Lehne, B. (Benjamin), Leach, I.M. (Irene Mateo), Drong, A. (Alexander), Abbott, J. (James), Wahl, S. (Simone), Tan, S.-T. (Sian-Tsung), Scott, W.R. (William R.), Campanella, G. (Gianluca), Chadeau-Hyam, M. (Marc), Afzal, U. (Uzma), Ahluwalia, T.S. (Tarunveer Singh), Bonder, M.J. (Marc), Chen, P. (Ping), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Esko, T. (Tõnu), Go, M.J. (Min Jin), Harris, S.E. (Sarah), Hartiala, J. (Jaana), Kasela, S. (Silva), Kasturiratne, A. (Anuradhani), Khor, C.C., Kleber, M.E. (Marcus), Li, H. (Huaixing), Mok, Z.Y. (Zuan Yu), Nakatochi, M. (Masahiro), Sapari, N.S. (Nur Sabrina), Saxena, R. (Richa), Stewart, A.F. (Alexandre F.), Stolk, L. (Lisette), Tabara, Y. (Yasuharu), Teh, A.L. (Ai Ling), Wu, Y. (Ying), Wu, J.-Y. (Jer-Yuarn), Zhang, Y. (Yi), Aits, I. (Imke), Da Silva Couto Alves, A. (Alexessander), Das, S. (Shikta), Dorajoo, R. (Rajkumar), CHopewell, J. (Jemma), Kim, Y.K. (Yun Kyoung), WKoivula, R. (Robert), Luan, J. (Jian'An), Lyytikäinen, L.-P. (Leo-Pekka), NNguyen, Q. (Quang), Pereira, M.A. (Mark A), Postmus, D. (Douwe), TRaitakari, O. (Olli), Scannell Bryan, M. (Molly), Scott, R.A. (Robert), Sorice, R., Tragante, V. (Vinicius), Traglia, M. (Michela), White, J. (Jon), Yamamoto, K. (Ken), Zhang, Y. (Yonghong), Adair, L.S. (Linda), Ahmed, A. (Alauddin), Akiyama, K. (Koichi), Asif, R. (Rasheed), Aung, T. (Tin), Barroso, I.E. (Inês), Bjonnes, A. (Andrew), Braun, T.R. (Timothy R.), Cai, H. (Hui), Chang, L.-C. (Li-Ching), Chen, C.-H., Cheng, C-Y. (Ching-Yu), Chong, Y.-S. (Yap-Seng), Collins, F.S. (Francis), Courtney, R. (Regina), Davies, G. (Gail), Delgado, G., Do, L.D. (Loi D.), Doevendans, P.A. (Pieter), Gansevoort, R.T. (Ron), Gao, Y. (Ying), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grewal, J. (Jagvir), Gu, D. (D.), SWander, G. (Gurpreet), Hartikainen, A.L., Hazen, S.L. (Stanley), He, J. (Jing), Heng, C.K. (Chew-Kiat), Hixso, E.J.A. (E. James Ames), Hofman, A. (Albert), Hsu, C. (Chris), Huang, W. (Wei), Husemoen, L.L.N. (Lise Lotte), Hwang, J.-Y. (Joo-Yeon), Ichihara, S. (Sahoko), Igase, M. (Michiya), Isono, M. (Masato), Justesen, J.M. (Johanne M.), Katsuya, T. (Tomohiro), GKibriya, M. (Muhammad), Kim, Y.J., Kishimoto, M. (Miyako), Koh, W.-P. (Woon-Puay), Kohara, K. (Katsuhiko), Kumari, M. (Meena), Kwek, K. (Kenneth), Lee, N.R. (Nanette), Lee, J. (Jeannette), Liao, J. (Jie), Lieb, W. (Wolfgang), Liewald, D.C.M. (David), Matsubara, T. (Tatsuaki), Matsushita, Y. (Yumi), Meitinger, T. (Thomas), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Mononen, K. (Kari), Müller-Nurasyid, M. (Martina), Nabika, T. (Toru), Nakashima, E. (Eitaro), Ng, H.K. (Hong Kiat), Nikus, K. (Kjell), Nutile, T., Ohkubo, T. (Takayoshi), Ohnaka, K. (Keizo), Parish, S. (Sarah), Paternoster, L. (Lavinia), Peng, H. (Hao), Peters, A. (Annette), TPham, S. (Son), Pinidiyapathirage, M.J. (Mohitha J.), Rahman, M. (Mahfuzar), Rakugi, H. (Hiromi), Rolandsson, O. (Olov), Rozario, M.A. (Michelle Ann), Ruggiero, D., Sala, C. (Cinzia), Sarju, R. (Ralhan), Shimokawa, K. (Kazuro), Snieder, H. (Harold), Sparsø, T. (Thomas), Spiering, W. (Wilko), Starr, J.M. (John), Stott, D.J. (David J.), OStram, D. (Daniel), Sugiyama, T. (Takao), Szymczak, S. (Silke), Tang, W.H.W. (W.H. Wilson), Tong, L. (Lin), Trompet, S. (Stella), Turjanmaa, V. (Väinö), Ueshima, H. (Hirotsugu), Uitterlinden, A.G. (André), Umemura, S. (Satoshi), Vaarasmaki, M. (Marja), Dam, R.M. (Rob Mvan), Gilst, W.H. (Wiek) van, Veldhuisen, D.J. (Dirk) van, Viikari, J. (Jorma), Waldenberger, M. (Melanie), Wang, Y. (Yiqin), Wang, A. (Aili), Wilson, R. (Rory), Wong, T.Y. (Tien Yin), Xiang, Y.-B. (Yong-Bing), Yamaguchi, S. (Shuhei), Ye, X. (Xingwang), Young, R. (Robin), Young, T.L. (Terri), Yuan, J.-M. (Jian-Min), Zhou, X. (Xueya), Asselbergs, F.W. (Folkert), Ciullo, M., Clarke, R. (Robert), Deloukas, P. (Panagiotis), Franke, A. (Andre), Paul, W.F. (W. Frank), Franks, S. (Steve), Friedlander, Y. (Yechiel), Gross, M.D. (Myron D.), Guo, Z. (Zhirong), Hansen, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Jørgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kajio, H. (Hiroshi), Kivimaki, M. (Mika), Lee, J.-Y. (Jong-Young), Lehtimäki, T. (Terho), Linneberg, A. (Allan), Miki, T. (Tetsuro), Pedersen, O. (Oluf), Samani, N.J. (Nilesh), Sørensen, T.I.A. (Thorkild), Takayanagi, R. (Ryoichi), Toniolo, D. (Daniela), Ahsan, H. (Habibul), Allayee, H. (Hooman), Chen, Y.-T. (Yuan-Tsong), Danesh, J. (John), Deary, I.J. (Ian), Franco, O.H. (Oscar), Franke, L. (Lude), THeijman, B. (Bastiaan), Holbrook, J.D. (Joanna D.), Isaacs, A.J. (Aaron), Kim, B.-J. (Bong-Jo), Lin, X. (Xu), Liu, J. (Jianjun), März, W. (Winfried), Metspalu, A. (Andres), Mohlke, K.L. (Karen), Sangher, K., Harambir, D. (Dharambir), Shu, X.-O. (Xiao-Ou), Meurs, J.B.J. (Joyce) van, Vithana, E.N. (Eranga), Wickremasinghe, A.R. (Ananda), Wijmenga, C. (Cisca), Wolffenbuttel, B.H.W. (Bruce H.W.), Yokota, M. (Mitsuhiro), Zheng, W. (Wei), Zhu, D. (Dingliang), Vineis, P. (Paolo), Kyrtopoulos, S.A. (Soterios A.), Kleinjans, J.C.S. (Jos C.S.), McCarthy, M.I. (Mark), Soong, R. (Richie), Gieger, C. (Christian), Scott, J. (James), Teo, Y.Y. (Yik Ying), He, J. (Jiang), Elliott, P. (Paul), Tai, E.S. (Shyong), Harst, P. (Pim) van der, Kooner, J.S. (Jaspal S.), Chambers, J.C. (John), Kato, N. (Norihiro), Loh, M. (Marie), Takeuchi, F. (Fumihiko), Verweij, N. (Niek), Wang, X. (Xu), Zhang, W. (Weihua), NKelly, T. (Tanika), Saleheen, D., Lehne, B. (Benjamin), Leach, I.M. (Irene Mateo), Drong, A. (Alexander), Abbott, J. (James), Wahl, S. (Simone), Tan, S.-T. (Sian-Tsung), Scott, W.R. (William R.), Campanella, G. (Gianluca), Chadeau-Hyam, M. (Marc), Afzal, U. (Uzma), Ahluwalia, T.S. (Tarunveer Singh), Bonder, M.J. (Marc), Chen, P. (Ping), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Esko, T. (Tõnu), Go, M.J. (Min Jin), Harris, S.E. (Sarah), Hartiala, J. (Jaana), Kasela, S. (Silva), Kasturiratne, A. (Anuradhani), Khor, C.C., Kleber, M.E. (Marcus), Li, H. (Huaixing), Mok, Z.Y. (Zuan Yu), Nakatochi, M. (Masahiro), Sapari, N.S. (Nur Sabrina), Saxena, R. (Richa), Stewart, A.F. (Alexandre F.), Stolk, L. (Lisette), Tabara, Y. (Yasuharu), Teh, A.L. (Ai Ling), Wu, Y. (Ying), Wu, J.-Y. (Jer-Yuarn), Zhang, Y. (Yi), Aits, I. (Imke), Da Silva Couto Alves, A. (Alexessander), Das, S. (Shikta), Dorajoo, R. (Rajkumar), CHopewell, J. (Jemma), Kim, Y.K. (Yun Kyoung), WKoivula, R. (Robert), Luan, J. (Jian'An), Lyytikäinen, L.-P. (Leo-Pekka), NNguyen, Q. (Quang), Pereira, M.A. (Mark A), Postmus, D. (Douwe), TRaitakari, O. (Olli), Scannell Bryan, M. (Molly), Scott, R.A. (Robert), Sorice, R., Tragante, V. (Vinicius), Traglia, M. (Michela), White, J. (Jon), Yamamoto, K. (Ken), Zhang, Y. (Yonghong), Adair, L.S. (Linda), Ahmed, A. (Alauddin), Akiyama, K. (Koichi), Asif, R. (Rasheed), Aung, T. (Tin), Barroso, I.E. (Inês), Bjonnes, A. (Andrew), Braun, T.R. (Timothy R.), Cai, H. (Hui), Chang, L.-C. (Li-Ching), Chen, C.-H., Cheng, C-Y. (Ching-Yu), Chong, Y.-S. (Yap-Seng), Collins, F.S. (Francis), Courtney, R. (Regina), Davies, G. (Gail), Delgado, G., Do, L.D. (Loi D.), Doevendans, P.A. (Pieter), Gansevoort, R.T. (Ron), Gao, Y. (Ying), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grewal, J. (Jagvir), Gu, D. (D.), SWander, G. (Gurpreet), Hartikainen, A.L., Hazen, S.L. (Stanley), He, J. (Jing), Heng, C.K. (Chew-Kiat), Hixso, E.J.A. (E. James Ames), Hofman, A. (Albert), Hsu, C. (Chris), Huang, W. (Wei), Husemoen, L.L.N. (Lise Lotte), Hwang, J.-Y. (Joo-Yeon), Ichihara, S. (Sahoko), Igase, M. (Michiya), Isono, M. (Masato), Justesen, J.M. (Johanne M.), Katsuya, T. (Tomohiro), GKibriya, M. (Muhammad), Kim, Y.J., Kishimoto, M. (Miyako), Koh, W.-P. (Woon-Puay), Kohara, K. (Katsuhiko), Kumari, M. (Meena), Kwek, K. (Kenneth), Lee, N.R. (Nanette), Lee, J. (Jeannette), Liao, J. (Jie), Lieb, W. (Wolfgang), Liewald, D.C.M. (David), Matsubara, T. (Tatsuaki), Matsushita, Y. (Yumi), Meitinger, T. (Thomas), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Mononen, K. (Kari), Müller-Nurasyid, M. (Martina), Nabika, T. (Toru), Nakashima, E. (Eitaro), Ng, H.K. (Hong Kiat), Nikus, K. (Kjell), Nutile, T., Ohkubo, T. (Takayoshi), Ohnaka, K. (Keizo), Parish, S. (Sarah), Paternoster, L. (Lavinia), Peng, H. (Hao), Peters, A. (Annette), TPham, S. (Son), Pinidiyapathirage, M.J. (Mohitha J.), Rahman, M. (Mahfuzar), Rakugi, H. (Hiromi), Rolandsson, O. (Olov), Rozario, M.A. (Michelle Ann), Ruggiero, D., Sala, C. (Cinzia), Sarju, R. (Ralhan), Shimokawa, K. (Kazuro), Snieder, H. (Harold), Sparsø, T. (Thomas), Spiering, W. (Wilko), Starr, J.M. (John), Stott, D.J. (David J.), OStram, D. (Daniel), Sugiyama, T. (Takao), Szymczak, S. (Silke), Tang, W.H.W. (W.H. Wilson), Tong, L. (Lin), Trompet, S. (Stella), Turjanmaa, V. (Väinö), Ueshima, H. (Hirotsugu), Uitterlinden, A.G. (André), Umemura, S. (Satoshi), Vaarasmaki, M. (Marja), Dam, R.M. (Rob Mvan), Gilst, W.H. (Wiek) van, Veldhuisen, D.J. (Dirk) van, Viikari, J. (Jorma), Waldenberger, M. (Melanie), Wang, Y. (Yiqin), Wang, A. (Aili), Wilson, R. (Rory), Wong, T.Y. (Tien Yin), Xiang, Y.-B. (Yong-Bing), Yamaguchi, S. (Shuhei), Ye, X. (Xingwang), Young, R. (Robin), Young, T.L. (Terri), Yuan, J.-M. (Jian-Min), Zhou, X. (Xueya), Asselbergs, F.W. (Folkert), Ciullo, M., Clarke, R. (Robert), Deloukas, P. (Panagiotis), Franke, A. (Andre), Paul, W.F. (W. Frank), Franks, S. (Steve), Friedlander, Y. (Yechiel), Gross, M.D. (Myron D.), Guo, Z. (Zhirong), Hansen, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Jørgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kajio, H. (Hiroshi), Kivimaki, M. (Mika), Lee, J.-Y. (Jong-Young), Lehtimäki, T. (Terho), Linneberg, A. (Allan), Miki, T. (Tetsuro), Pedersen, O. (Oluf), Samani, N.J. (Nilesh), Sørensen, T.I.A. (Thorkild), Takayanagi, R. (Ryoichi), Toniolo, D. (Daniela), Ahsan, H. (Habibul), Allayee, H. (Hooman), Chen, Y.-T. (Yuan-Tsong), Danesh, J. (John), Deary, I.J. (Ian), Franco, O.H. (Oscar), Franke, L. (Lude), THeijman, B. (Bastiaan), Holbrook, J.D. (Joanna D.), Isaacs, A.J. (Aaron), Kim, B.-J. (Bong-Jo), Lin, X. (Xu), Liu, J. (Jianjun), März, W. (Winfried), Metspalu, A. (Andres), Mohlke, K.L. (Karen), Sangher, K., Harambir, D. (Dharambir), Shu, X.-O. (Xiao-Ou), Meurs, J.B.J. (Joyce) van, Vithana, E.N. (Eranga), Wickremasinghe, A.R. (Ananda), Wijmenga, C. (Cisca), Wolffenbuttel, B.H.W. (Bruce H.W.), Yokota, M. (Mitsuhiro), Zheng, W. (Wei), Zhu, D. (Dingliang), Vineis, P. (Paolo), Kyrtopoulos, S.A. (Soterios A.), Kleinjans, J.C.S. (Jos C.S.), McCarthy, M.I. (Mark), Soong, R. (Richie), Gieger, C. (Christian), Scott, J. (James), Teo, Y.Y. (Yik Ying), He, J. (Jiang), Elliott, P. (Paul), Tai, E.S. (Shyong), Harst, P. (Pim) van der, Kooner, J.S. (Jaspal S.), and Chambers, J.C. (John)

Abstract

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10 -11 to 5.0 × 10 -21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10 -6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Published
2015
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34. CHROMOSOME 9P21 LOCUS AND ANGIOGRAPHIC CORONARY ARTERY DISEASE BURDEN: A COLLABORATIVE META-ANALYSIS

Author

Chan, K, Patel, RS, Newcombe, P, Nelson, CP, Qasim, A, Epstein, SE, Burnett, S, Vaccarino, VL, Zafari, AM, Shah, SH, Anderson, JL, Carlquist, JF, Hartiala, J, Allayee, H, Hinohara, K, Lee, BS, Erl, A, Ellis, KL, Goel, A, Schaefer, AS, Mokhtari, NE, Goldstein, BA, Hlatky, MA, Go, AS, Shen, GQ, Gong, Y, Pepine, C, Laxton, RC, Wittaker, JC, Tang, WHW, Johnson, JA, Wang, QK, Assimes, TL, Noethlings, U, Farrall, M, Watkins, H, Richards, AM, Cameron, VA, Muendlein, A, Drexel, H, Koch, W, Park, JE, Kimura, A, Shen, WF, Simpson, IA, Hazen, SL, Horne, BD, Hauser, ER, Quyyumi, AA, Reilly, MP, Samani, NJ, and Ye, S

Published
2013

36. New gene functions in megakaryopoiesis and platelet formation

Author

Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, Serbanovic-Canic J, Elling U, Goodall AH, Labrune Y, Lopez LM, Mxe4gi R, Meacham S, Okada Y, Pirastu N, Sorice R, Teumer A, Voss K, Zhang W, Ramirez-Solis R, Bis JC, Ellinghaus D, Gxf6gele M, Hottenga JJ, Langenberg C, Kovacs P, O'Reilly PF, Shin SY, Esko T, Hartiala J, Kanoni S, Penninger J, and et al

Published
2011

37. Circulating N-terminal brain natriuretic peptide and cardiac function in response to acute systemic hypoxia in healthy humans

Author

Heinonen, I.H.A. (Ilkka), Luotolahti, M. (Matti), Vuolteenaho, O. (Olli), Nikinmaa, M. (Mikko), Saraste, A. (Antti), Hartiala, J. (Jaakko), Koskenvuo, J. (Juha), Knuuti, J. (Juhani), Arjamaa, O. (Olli), Heinonen, I.H.A. (Ilkka), Luotolahti, M. (Matti), Vuolteenaho, O. (Olli), Nikinmaa, M. (Mikko), Saraste, A. (Antti), Hartiala, J. (Jaakko), Koskenvuo, J. (Juha), Knuuti, J. (Juhani), and Arjamaa, O. (Olli)

Abstract

Background: As it remains unclear whether hypoxia of cardiomyocytes could trigger the release of brain natriuretic peptide (BNP) in humans, we investigated whether breathing normobaric hypoxic gas mixture increases the circulating NT-proBNP in healthy male subjects.Methods: Ten healthy young men (age 29 ± 5 yrs, BMI 24.7 ± 2.8 kg/m2) breathed normobaric hypoxic gas mixture (11% O2/89% N2) for one hour. Venous blood samples were obtained immediately before, during, and 2 and 24 hours after hypoxic exposure. Cardiac function and flow velocity profile in the middle left anterior descending coronary artery (LAD) were measured by Doppler echocardiography.Results: Arterial oxygen saturation decreased steadily from baseline value of 99 ± 1% after the initiation hypoxia challenge and reached steady-state level of 73 ± 6% within 20-30 minutes. Cardiac output increased from 6.0 ± 1.2 to 8.1 ± 1.6 L/min and ejection fraction from 67 ± 4% to 75 ± 6% (both p < 0.001). Peak diastolic flow velocity in the LAD increased from 0.16 ± 0.04 to 0.28 ± 0.07 m/s, while its diameter remained unchanged. In the whole study group, NT-proBNP was similar to baseline (60 ± 32 pmol/ml) at all time points. However, at 24 h, concentration of NT-proBNP was higher (34 ± 18%) in five subjects and lower (17 ± 17%), p = 0.002 between the groups) in fi

Published
2014
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38. Known SNPs in ADAMTS7, the 9p21 region and UBE2E interact with type 2 diabetes status to modify the risk of coronary artery disease in large populations

Author

van Zuydam, N. R., Voight, B., Ladenvall, C., Strawbridge, R., Willems, S., Hartiala, J., Vlacholpoulou, E., Mihailov, E., Kwee, L., Qu, L., Goel, A., Kumar, Jitender, Kanoni, S., van Zuydam, N. R., Voight, B., Ladenvall, C., Strawbridge, R., Willems, S., Hartiala, J., Vlacholpoulou, E., Mihailov, E., Kwee, L., Qu, L., Goel, A., Kumar, Jitender, and Kanoni, S.

Published
2013

39. Seventy-five genetic loci influencing the human red blood cell

Author

van der Harst, P., Zhang, W., Mateo Leach, I., Rendon, A., Verweij, N., Sehmi, J., Paul, D.S., Elling, U., Allayee, H., Li, X., Radhakrishnan, A., Tan, S.T., Voss, K., Weichenberger, C.X., Albers, C.A., Al-Hussani, A., Asselbergs, F.W., Ciullo, M., Danjou, F., Dina, C., Esko, T., Evans, D.M., Franke, L., Gogele, M., Hartiala, J., Hersch, M., Holm, H., Hottenga, J.J., Kanoni, S., Kleber, M.E., Lagou, V., Langenberg, C., Lopez, L.M., Lyytikainen, L.P., Melander, O., Murgia, F., Nolte, I.M., O'Reilly, P.F., Padmanabhan, S., Parsa, A., Pirastu, N., Porcu, E., Portas, L., Prokopenko, I., Ried, J.S., Shin, S.Y., Tang, C.S., Teumer, A., Traglia, M., Ulivi, S., Westra, H.J., Yang, J., Zhao, J.H., Anni, F., Abdellaoui, A., Attwood, A., Balkau, B., Bandinelli, S., Bastardot, F., Benyamin, B., Boehm, B.O., Cookson, W.O., Das, D, de Bakker, P.I., de Boer, R.A., de Geus, E.J., de Moor, M.H., Dimitriou, M., Domingues, F.S., Doring, A., Engstrom, G., Eyjolfsson, G.I., Ferrucci, L., Fischer, K., Galanello, R., Garner, S.F., Genser, B., Gibson, Q.D., Girotto, G., Gudbjartsson, D.F., Harris, S.E., Hartikainen, A.L., Hastie, C.E., Hedblad, B., Illig, T., Jolley, J., Kahonen, M., Kema, I.P., Kemp, J.P., Liang, L., Lloyd-Jones, H., Loos, R.J., Meacham, S., Medland, S.E., Meisinger, C., Memari, Y., Mihailov, E., Miller, K., Moffatt, M.F., Nauck, M., et al., van der Harst, P., Zhang, W., Mateo Leach, I., Rendon, A., Verweij, N., Sehmi, J., Paul, D.S., Elling, U., Allayee, H., Li, X., Radhakrishnan, A., Tan, S.T., Voss, K., Weichenberger, C.X., Albers, C.A., Al-Hussani, A., Asselbergs, F.W., Ciullo, M., Danjou, F., Dina, C., Esko, T., Evans, D.M., Franke, L., Gogele, M., Hartiala, J., Hersch, M., Holm, H., Hottenga, J.J., Kanoni, S., Kleber, M.E., Lagou, V., Langenberg, C., Lopez, L.M., Lyytikainen, L.P., Melander, O., Murgia, F., Nolte, I.M., O'Reilly, P.F., Padmanabhan, S., Parsa, A., Pirastu, N., Porcu, E., Portas, L., Prokopenko, I., Ried, J.S., Shin, S.Y., Tang, C.S., Teumer, A., Traglia, M., Ulivi, S., Westra, H.J., Yang, J., Zhao, J.H., Anni, F., Abdellaoui, A., Attwood, A., Balkau, B., Bandinelli, S., Bastardot, F., Benyamin, B., Boehm, B.O., Cookson, W.O., Das, D, de Bakker, P.I., de Boer, R.A., de Geus, E.J., de Moor, M.H., Dimitriou, M., Domingues, F.S., Doring, A., Engstrom, G., Eyjolfsson, G.I., Ferrucci, L., Fischer, K., Galanello, R., Garner, S.F., Genser, B., Gibson, Q.D., Girotto, G., Gudbjartsson, D.F., Harris, S.E., Hartikainen, A.L., Hastie, C.E., Hedblad, B., Illig, T., Jolley, J., Kahonen, M., Kema, I.P., Kemp, J.P., Liang, L., Lloyd-Jones, H., Loos, R.J., Meacham, S., Medland, S.E., Meisinger, C., Memari, Y., Mihailov, E., Miller, K., Moffatt, M.F., and Nauck, M., et al.

Abstract

Item does not contain fulltext, Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

Published
2012

40. Genome-Wide association study of coronary heart disease and its risk factors in 8,090 african americans: The nhlbi CARe project

Author

Lettre, G, Palmer, CD, Young, T, Ejebe, KG, Allayee, H, Benjamin, EJ, Bennett, F, Bowden, DW, Chakravarti, A, Dreisbach, A, Farlow, DN, Folsom, AR, Fornage, M, Forrester, T, Fox, E, Haiman, CA, Hartiala, J, Harris, TB, Hazen, SL, Heckbert, SR, Henderson, BE, Hirschhorn, JN, Keating, BJ, Kritchevsky, SB, Larkin, E, Li, M, Rudock, ME, McKenzie, CA, Meigs, JB, Meng, YA, Mosley, TH, Newman, AB, Newton-Cheh, CH, Paltoo, DN, Papanicolaou, GJ, Patterson, N, Post, WS, Psaty, BM, Qasim, AN, Qu, L, Rader, DJ, Redline, S, Reilly, MP, Reiner, AP, Rich, SS, Rotter, JI, Liu, Y, Shrader, P, Siscovick, DS, Tang, WHW, Taylor, HA, Tracy, RP, Vasan, RS, Waters, KM, Wilks, R, Wilson, JG, Fabsitz, RR, Gabriel, SB, Kathiresan, S, Boerwinkle, E, Lettre, G, Palmer, CD, Young, T, Ejebe, KG, Allayee, H, Benjamin, EJ, Bennett, F, Bowden, DW, Chakravarti, A, Dreisbach, A, Farlow, DN, Folsom, AR, Fornage, M, Forrester, T, Fox, E, Haiman, CA, Hartiala, J, Harris, TB, Hazen, SL, Heckbert, SR, Henderson, BE, Hirschhorn, JN, Keating, BJ, Kritchevsky, SB, Larkin, E, Li, M, Rudock, ME, McKenzie, CA, Meigs, JB, Meng, YA, Mosley, TH, Newman, AB, Newton-Cheh, CH, Paltoo, DN, Papanicolaou, GJ, Patterson, N, Post, WS, Psaty, BM, Qasim, AN, Qu, L, Rader, DJ, Redline, S, Reilly, MP, Reiner, AP, Rich, SS, Rotter, JI, Liu, Y, Shrader, P, Siscovick, DS, Tang, WHW, Taylor, HA, Tracy, RP, Vasan, RS, Waters, KM, Wilks, R, Wilson, JG, Fabsitz, RR, Gabriel, SB, Kathiresan, S, and Boerwinkle, E

Abstract

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

Published
2011

41. 126 CHROMOSOME 9P21 LOCUS AND ANGIOGRAPHIC CORONARY ARTERY DISEASE BURDEN: A COLLABORATIVE META-ANALYSIS

Author

Chan, K, primary, Patel, R S, additional, Newcombe, P, additional, Nelson, C P, additional, Qasim, A, additional, Epstein, S E, additional, Burnett, S, additional, Vaccarino, V L, additional, Zafari, A M, additional, Shah, S H, additional, Anderson, J L, additional, Carlquist, J F, additional, Hartiala, J, additional, Allayee, H, additional, Hinohara, K, additional, Lee, B S, additional, Erl, A, additional, Ellis, K L, additional, Goel, A, additional, Schaefer, A S, additional, Mokhtari, N E, additional, Goldstein, B A, additional, Hlatky, M A, additional, Go, A S, additional, Shen, G Q, additional, Gong, Y, additional, Pepine, C, additional, Laxton, R C, additional, Wittaker, J C, additional, Tang, W H W, additional, Johnson, J A, additional, Wang, Q K, additional, Assimes, T L, additional, Nöthlings, U, additional, Farrall, M, additional, Watkins, H, additional, Richards, A M, additional, Cameron, V A, additional, Muendlein, A, additional, Drexel, H, additional, Koch, W, additional, Park, J E, additional, Kimura, A, additional, Shen, W F, additional, Simpson, I A, additional, Hazen, S L, additional, Horne, B D, additional, Hauser, E R, additional, Quyyumi, A A, additional, Reilly, M P, additional, Samani, N J, additional, and Ye, S, additional

Published
2013
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42. Poster Session 5: Saturday 10 December 2011, 08:30-12:30 * Location: Poster Area

Author

Gong, L., primary, Ye, Z., additional, Zeng, Z., additional, Xia, M., additional, Zhong, Y., additional, Yao, Y., additional, Lee, E., additional, Ionescu, A., additional, Dwivedi, G., additional, Mahadevan, G., additional, Jiminez, D., additional, Frenneaux, M., additional, Steeds, R., additional, Moore, C., additional, Samad, Z., additional, Jackson, K., additional, Castellucci, J., additional, Kisslo, J., additional, Von Ramm, O., additional, D'ascenzi, F., additional, Zaca', V., additional, Cameli, M., additional, Lisi, M., additional, Natali, B., additional, Malandrino, A., additional, Mondillo, S., additional, Barbier, P., additional, Guerrini, U., additional, Franzosi, M., additional, Castiglioni, L., additional, Nobili, E., additional, Colazzo, F., additional, Li Causi, T., additional, Sironi, L., additional, Tremoli, E., additional, Clausen, H., additional, Macdonald, S., additional, Basaggianis, C., additional, Newton, J., additional, Bennati, E., additional, Reccia, R., additional, Bigio, E., additional, Maccherini, M., additional, Chiavarelli, M., additional, Henein, M., additional, Floria, M., additional, Jamart, J., additional, Arsenescu Georgescu, C., additional, Mantovani, F., additional, Barbieri, A., additional, Bursi, F., additional, Valenti, C., additional, Quaglia, M., additional, Modena, M., additional, Kutty, S., additional, Gribben, P., additional, Padiyath, A., additional, Polak, A., additional, Scott, C., additional, Waiss, M., additional, Danford, D., additional, Bech-Hanssen, O., additional, Selimovic, N., additional, Rundqvist, B., additional, Schmiedel, L., additional, Hohmann, C., additional, Katzke, S., additional, Haacke, K., additional, Rauwolf, T., additional, Strasser, R., additional, Tumasyan, L. R., additional, Adamyan, K., additional, Kosmala, W., additional, Derzhko, R., additional, Przewlocka-Kosmala, M., additional, Mysiak, A., additional, Stachowska, B., additional, Jedrzejuk, D., additional, Bednarek-Tupikowska, G., additional, Chrzanowski, L., additional, Kasprzak, J., additional, Wojciechowska, C., additional, Wita, K., additional, Busz-Papiez, B., additional, Gasior, Z., additional, Mizia-Stec, K., additional, Kukulski, T., additional, Gosciniak, P., additional, Sinkiewicz, W., additional, Moelmen, H., additional, Stoylen, A., additional, Thorstensen, A., additional, Torp, H., additional, Dalen, H., additional, Groves, A., additional, Nicholson, G., additional, Lopez, L., additional, Goh, C.-W., additional, Ahn, H., additional, Byun, Y., additional, Kim, J., additional, Park, J., additional, Lee, J., additional, Kim, B., additional, Rhee, K., additional, Kim, K., additional, Yoon, H., additional, Hong, Y., additional, Park, H., additional, Ahn, Y., additional, Jeong, M., additional, Cho, J., additional, Kang, J., additional, Grapsa, J., additional, Dawson, D., additional, Karfopoulos, K., additional, Jakaj, G., additional, Punjabi, P., additional, Nihoyannopoulos, P., additional, Ruisanchez Villar, C., additional, Lerena Saenz, P., additional, Gonzalez Vilchez, F., additional, Gonzalez Fernandez, C., additional, Zurbano Goni, F., additional, Cifrian Martinez, J., additional, Mons Lera, R., additional, Ruano Calvo, J., additional, Martin Duran, R., additional, Vazquez De Prada Tiffe, J., additional, Pietrzak, R., additional, Werner, B., additional, Voillot, D., additional, Huttin, O., additional, Zinzius, P., additional, Schwartz, J., additional, Sellal, J., additional, Lemoine, S., additional, Christophe, C., additional, Popovic, B., additional, Juilliere, Y., additional, Selton-Suty, C., additional, Ishii, K., additional, Furukawa, A., additional, Nagai, T., additional, Kataoka, K., additional, Seino, Y., additional, Shimada, K., additional, Yoshikawa, J., additional, Tekkesin, A., additional, Yildirimturk, O., additional, Tayyareci, Y., additional, Yurdakul, S., additional, Aytekin, S., additional, Jaroch, J., additional, Loboz-Grudzien, K., additional, Bociaga, Z., additional, Kowalska, A., additional, Kruszynska, E., additional, Wilczynska, M., additional, Dudek, K., additional, Kakihara, R., additional, Naruse, C., additional, Hironaka, H., additional, Tsuzuku, T., additional, Cucchini, U., additional, Muraru, D., additional, Badano, L., additional, Solda', E., additional, Tuveri, M., additional, Al Nono, O., additional, Sarais, C., additional, Iliceto, S., additional, Santos, L., additional, Cortez-Dias, N., additional, Ribeiro, S., additional, Goncalves, S., additional, Jorge, C., additional, Carrilho-Ferreira, P., additional, Silva, D., additional, Silva-Marques, J., additional, Lopes, M., additional, Diogo, A., additional, Hristova, K., additional, Vassilev, D., additional, Pavlov, P., additional, Katova, T., additional, Simova, I., additional, Kostova, V., additional, Esposito, R., additional, Santoro, A., additional, Schiano Lomoriello, V., additional, Raia, R., additional, De Palma, D., additional, Dores, E., additional, De Simone, G., additional, Galderisi, M., additional, Zaborska, B., additional, Makowska, E., additional, Pilichowska, E., additional, Maciejewski, P., additional, Bednarz, B., additional, Wasek, W., additional, Stec, S., additional, Budaj, A., additional, Spinelli, L., additional, Morisco, C., additional, Assante Di Panzillo, E., additional, Crispo, S., additional, Di Marino, S., additional, Trimarco, B., additional, Farina, F., additional, Innelli, P., additional, Rapacciuolo, A., additional, Polgar, B., additional, Banyai, F., additional, Rokusz, L., additional, Tomcsanyi, I., additional, Vaszily, M., additional, Nieszner, E., additional, Borsanyi, T., additional, Kerecsen, G., additional, Preda, I., additional, Kiss, R. 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M. P., additional, Eising, J. B., additional, Uiterwaal, C., additional, Van Der Ent, C. K., additional, Meijboom, F. J., additional, Shang, Q., additional, Tam, L., additional, Sun, J., additional, Sanderson, J., additional, Zhang, Q., additional, Li, E., additional, Yu, C., additional, Arroyo Ucar, E., additional, De La Rosa Hernandez, A., additional, Hernandez Garcia, C., additional, Jorge Perez, P., additional, Lacalzada Almeida, J., additional, Jimenez Rivera, J., additional, Duque Garcia, A., additional, Barragan Acea, A., additional, Laynez Cerdena, I., additional, Kaldararova, M., additional, Simkova, I., additional, Pacak, J., additional, Tittel, P., additional, Masura, J., additional, Tadic, M., additional, Ivanovic, B., additional, Zlatanovic, M., additional, Damjanov, N., additional, Maggiolini, S., additional, Gentile, G., additional, Bozzano, A., additional, Suraci, S., additional, Meles, E., additional, Carbone, C., additional, Tempesta, A., additional, Malafronte, C., additional, Piatti, L., additional, Achilli, F., additional, Luijendijk, P., additional, Stevens, A., additional, De Bruin-Bon, H., additional, Vriend, J., additional, Van Den Brink, R., additional, Vliegen, H., additional, Mulder, B., additional, Chow, V., additional, Ng, A., additional, Chung, T., additional, Kritharides, L., additional, Iancu, M., additional, Serban, M., additional, Craciunescu, I., additional, Hodo, A., additional, Ghiorghiu, I., additional, Popescu, B., additional, Ginghina, C., additional, Styczynski, G., additional, Szmigielski, C. A., additional, Kaczynska, A., additional, Leszczynski, J., additional, Rosinski, G., additional, Kuch-Wocial, A., additional, Slavich, M., additional, Ancona, M., additional, Fisicaro, A., additional, Oppizzi, M., additional, Marone, E., additional, Bertoglio, L., additional, Melissano, G., additional, Margonato, A., additional, Chiesa, R., additional, Agricola, E., additional, Mohammed, M., additional, Cusma-Piccione, M., additional, Piluso, S., additional, Arcidiaco, S., additional, Nava, R., additional, Giuffre, R., additional, Ciraci, L., additional, Ferro, M., additional, Uusitalo, V., additional, Luotolahti, M., additional, Pietila, M., additional, Wendelin-Saarenhovi, M., additional, Hartiala, J., additional, Saraste, M., additional, Knuuti, J., additional, Saraste, A., additional, Kochanowski, J., additional, Scislo, P., additional, Piatkowski, R., additional, Grabowski, M., additional, Marchel, M., additional, Roik, M., additional, Kosior, D., additional, Opolski, G., additional, Bartko, P. E., additional, Graf, S., additional, Khorsand, A., additional, Rosenhek, R., additional, Burwash, I., additional, Beanlands, R., additional, Baumgartner, H., additional, Mundigler, G., additional, Kudrnova, S., additional, Apor, A., additional, Huttl, H., additional, Mori, F., additional, Santoro, G., additional, Oddo, A., additional, Rosso, G., additional, Meucci, F., additional, Pieri, F., additional, Squillantini, G., additional, Gensini, G., additional, Postula, M., additional, Park, D.-G., additional, Hong, J.-Y., additional, Kim, S.-E., additional, Lee, J.-H., additional, Han, K.-R., additional, Oh, D.-J., additional, Dal Bianco, L., additional, Beraldo, M., additional, Peluso, D., additional, Al Mamary, A., additional, Aggeli, C., additional, Felekos, I., additional, Poulidakis, E., additional, Pietri, P., additional, Roussakis, G., additional, Siasos, G., additional, Stefanadis, C., additional, Hoshiba, H., additional, Miyasaka, C., additional, Sato, H., additional, Yamanaka, A., additional, Lilli, A., additional, Baratto, M., additional, Magnacca, M., additional, Comella, A., additional, Poddighe, R., additional, Talini, E., additional, Canale, M., additional, Chioccioli, M., additional, Del Meglio, J., additional, Casolo, G., additional, Kuznetsov, V. A., additional, Melnikov, N. N., additional, Krinochkin, D. V., additional, Calin, A., additional, Enache, R., additional, Beladan, C., additional, Rosca, M., additional, Lupascu, L., additional, Purcarea, F., additional, Calin, C., additional, Gurzun, M., additional, Dulgheru, R., additional, Ciobanu, A., additional, Magda, S., additional, Mihaila, S., additional, Rimbas, R., additional, Margulescu, A., additional, Cinteza, M., additional, Vinereanu, D., additional, Sumin, A. N., additional, Arhipov, O., additional, Yoon, J., additional, Moon, J., additional, Rim, S., additional, Nyktari, E., additional, Patrianakos, A., additional, Solidakis, G., additional, Psathakis, E., additional, Parthenakis, F., additional, Vardas, P., additional, Kordybach, M., additional, Kowalski, M., additional, Kowalik, E., additional, Hoffman, P., additional, Nagy, K. V., additional, Kutyifa, V., additional, Edes, E., additional, Merkely, B., additional, Gerlach, A., additional, Rost, C., additional, Schmid, M., additional, Rost, M., additional, Flachskampf, F., additional, Daniel, W., additional, Breithardt, O., additional, Altekin, E., additional, Karakas, S., additional, Yanikoglu, A., additional, Er, A., additional, Baktir, A., additional, Demir, I., additional, Deger, N., additional, Klitsie, L., additional, Hazekamp, M., additional, Roest, A., additional, Van Der Hulst, A., additional, Gesink- Van Der Veer, B., additional, Kuipers, I., additional, Blom, N., additional, Ten Harkel, A., additional, Farsalinos, K., additional, Tsiapras, D., additional, Kyrzopoulos, S., additional, Avramidou, E., additional, Vasilopoulou, D., additional, Voudris, V., additional, Florianczyk, T., additional, Kalinowski, M., additional, Szulik, M., additional, Streb, W., additional, Rybus-Kalinowska, B., additional, Sliwinska, A., additional, Stabryla, J., additional, Kukla, M., additional, Nowak, J., additional, Kalarus, Z., additional, Florescu, M., additional, Mihalcea, D., additional, Magda, L., additional, Suran, B., additional, Enescu, O., additional, Mincu, R., additional, Salerno, G., additional, Scognamiglio, G., additional, D'andrea, A., additional, Dinardo, G., additional, Gravino, R., additional, Sarubbi, B., additional, Disalvo, G., additional, Liao, J.-N., additional, Sung, S., additional, Chen, C., additional, Park, S., additional, Shin, S., additional, Kim, M., additional, Shim, S., additional, Helvacioglu, F., additional, Ulusoy, O., additional, Duran, C., additional, Kirschner, R., additional, Simor, T., additional, Ambrosio, G., additional, Tran, T., additional, Raman, S., additional, Vidal Perez, R. C., additional, Carreras, F., additional, Leta, R., additional, Pujadas, S., additional, Barros, A., additional, Hidalgo, A., additional, Alomar, X., additional, Pons-Llado, G., additional, Olofsson, M., additional, Boman, K., additional, Ledakowicz-Polak, A., additional, Polak, L., additional, Zielinska, M., additional, Fontana, A., additional, Schirone, V., additional, Mauro, A., additional, Zambon, A., additional, Giannattasio, C., additional, Trocino, G., additional, Dekleva, M., additional, Dungen, H., additional, Inkrot, S., additional, Gelbrich, G., additional, Suzic Lazic, J., additional, Kleut, M., additional, Markovic Nikolic, N., additional, Waagstein, F., additional, Khoor, S., additional, Balogh, N., additional, Simon, I., additional, Fugedi, K., additional, Kovacs, I., additional, Khoor, M., additional, Florian, G., additional, Kocsis, A., additional, Szuszai, T., additional, O'driscoll, J., additional, Saha, A., additional, Smith, R., additional, Gupta, S., additional, Lenkey, Z., additional, Gaszner, B., additional, Illyes, M., additional, Sarszegi, Z., additional, Horvath, I. G., additional, Magyari, B., additional, Molnar, F., additional, Cziraki, A., additional, Elnoamany, M. F., additional, Badran, H., additional, Ebraheem, H., additional, Reda, A., additional, and Elsheekh, N., additional

Published
2011
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43. Resting coronary flow velocity in the functional evaluation of coronary artery stenosis: study on sequential use of computed tomography angiography and transthoracic Doppler echocardiography

Author

Joutsiniemi, E., primary, Saraste, A., additional, Pietila, M., additional, Ukkonen, H., additional, Kajander, S., additional, Maki, M., additional, Koskenvuo, J., additional, Airaksinen, J., additional, Hartiala, J., additional, Saraste, M., additional, and Knuuti, J., additional

Published
2011
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45. Cardiac Positron Emission Tomography/Computed Tomography Imaging Accurately Detects Anatomically and Functionally Significant Coronary Artery Disease

Author

Kajander, S., primary, Joutsiniemi, E., additional, Saraste, M., additional, Pietilä, M., additional, Ukkonen, H., additional, Saraste, A., additional, Sipilä, H.T., additional, Teräs, M., additional, Mäki, M., additional, Airaksinen, J., additional, Hartiala, J., additional, and Knuuti, J., additional

Published
2010
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50. Population-Based Twin Study of the Effects of Migration From Finland to Sweden on Endothelial Function and Intima-Media Thickness

Author

Jartti, L., primary, Rönnemaa, T., additional, Kaprio, J., additional, Järvisalo, M.J., additional, Toikka, J.O., additional, Marniemi, J., additional, Hammar, N., additional, Alfredsson, L., additional, Saraste, M., additional, Hartiala, J., additional, Koskenvuo, M., additional, and Raitakari, O.T., additional

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2002
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