303 results on '"Pare, G"'
Search Results
2. THE CLINICAL UTILITY AND ANCESTRAL DIVERSITY OF POLYGENIC RISK SCORES IN CARDIOMETABOLIC DISEASE RISK PREDICTION
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Phulka, J., primary, Ashraf, M., additional, Bajwa, B., additional, Pare, G., additional, and Laksman, Z., additional
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- 2023
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3. Genetic predisposition to high blood pressure and out-of-office hypertension: insights from a population sample in Liechtenstein
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Narula, S, primary, Mohammadi-Shemirani, P M, additional, Aeschbacher, S, additional, Chong, M R, additional, Le, A, additional, Theriault, S, additional, Grossman, K, additional, Pare, G, additional, Risch, L, additional, Risch, M, additional, and Conen, D, additional
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- 2023
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4. PB0137 Diagnostic and Predictive Value of Circulating MicroRNAs and their Regulation of the BDNF Signaling Pathway in Stroke Patients
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Eyileten, C., primary, Nowak, A., additional, Wicik, Z., additional, De Rosa, S., additional, Chong, M., additional, Pare, G., additional, and Potuła, M., additional
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- 2023
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5. Once versus twice daily aspirin after coronary bypass surgery: a randomized trial
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Paikin, J.S., Hirsh, J., Ginsberg, J.S., Weitz, J.I., Chan, N.C., Whitlock, R.P., Pare, G., and Eikelboom, J.W.
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- 2017
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6. The current state and future of cardiometabolic polygenic risk scores in European and non-European population cohorts
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Phulka, J, primary, Ashraf, M, additional, Bajwa, B, additional, Pare, G, additional, and Laksman, Z, additional
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- 2023
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7. IDF2022-0682 If you are diabetic, you might pick some things differently: diabetes self-management for seniors in Ontario, Canada
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Camargo-Plazas, P., primary, Alvarado, B., additional, Pare, G., additional, Robertson, M., additional, Costa, I., additional, and Duhn, L., additional
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- 2023
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8. Use of genetic data to guide therapy in arterial disease
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Ross, S., Nejat, S., and Paré, G.
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- 2015
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9. Multiple daily doses of acetyl‐salicylic acid (ASA) overcome reduced platelet response to once‐daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial
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Paikin, J.S., Hirsh, J., Ginsberg, J.S., Weitz, J.I., Chan, N.C., Whitlock, R.P., Pare, G., Johnston, M., and Eikelboom, J.W.
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- 2015
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10. Active metabolite concentration of clopidogrel in patients taking different doses of aspirin: results of the interaction trial
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Liang, Y., Hirsh, J., Weitz, J.I., Sloane, D., Gao, P., Pare, G., Zhu, J., and Eikelboom, J.W.
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- 2015
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11. Phosphoinositide 3-kinase and airway infections in severe asthmatics
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Bhalla, A, primary, Radford, K, additional, Zhang, K, additional, Brautigam, Z, additional, Huang, C, additional, Kjarsgaard, M, additional, Lavigne, N, additional, Svenningsen, S, additional, Pare, G, additional, Mukherjee, M, additional, and Nair, P, additional
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- 2022
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12. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke
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Jaworek, T, Xu, H, Gaynor, BJ, Cole, JW, Rannikmae, K, Stanne, TM, Tomppo, L, Abedi, V, Amouyel, P, Armstrong, ND, Attia, J, Bell, S, Benavente, OR, Boncoraglio, GB, Butterworth, A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez, J, Chen, Z, Chong, M, Cruchaga, C, Cushman, M, Danesh, J, Debette, S, Duggan, DJ, Durda, JP, Engstrom, G, Enzinger, C, Faul, JD, Fecteau, NS, Fernandez-Cadenas, I, Gieger, C, Giese, A-K, Grewal, RP, Grittner, U, Havulinna, AS, Heitsch, L, Hochberg, MC, Holliday, E, Hu, J, Ilinca, A, INVENT Consortium, Irvin, MR, Jackson, RD, Jacob, MA, Janssen, RR, Jimenez-Conde, J, Johnson, JA, Kamatani, Y, Kardia, SL, Koido, M, Kubo, M, Lange, L, Lee, J-M, Lemmens, R, Levi, CR, Li, J, Li, L, Lin, K, Lopez, H, Luke, S, Maguire, J, McArdle, PF, McDonough, CW, Meschia, JF, Metso, T, Muller-Nurasyid, M, O'Connor, TD, O'Donnell, M, Peddareddygari, LR, Pera, J, Perry, JA, Peters, A, Putaala, J, Ray, D, Rexrode, K, Ribases, M, Rosand, J, Rothwell, PM, Rundek, T, Ryan, KA, Sacco, RL, Salomaa, V, Sanchez-Mora, C, Schmidt, R, Sharma, P, Slowik, A, Smith, JA, Smith, NL, Wassertheil-Smoller, S, Soederholm, M, Stine, OC, Strbian, D, Sudlow, CL, Tatlisumak, T, Terao, C, Thijs, V, Torres-Aguila, NP, Tregouet, D-A, Tuladhar, AM, Veldink, JH, Walters, RG, Weir, DR, Woo, D, Worrall, BB, Hong, CC, Ross, O, Zand, R, Leeuw, F-ED, Lindgren, AG, Pare, G, Anderson, CD, Markus, HS, Jern, C, Malik, R, Dichgans, M, Mitchell, BD, Kittner, SJ, and Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC)
- Subjects
Neurology & Neurosurgery ,1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences - Abstract
BACKGROUND AND OBJECTIVES: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. METHODS: We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. RESULTS: We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). DISCUSSION: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
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- 2022
13. Stroke genetics informs drug discovery and risk prediction across ancestries
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Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S
- Abstract
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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- 2022
14. Stroke genetics informs drug discovery and risk prediction across ancestries (vol 611, pg 115, 2022)
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Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, and Debette, S
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- 2022
15. Using Case Study Research to Build Theories of IT Implementation
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Paré, G., Elam, J. J., Lee, Allen S., editor, Liebenau, Jonathan, editor, and DeGross, Janice I., editor
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- 1997
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16. B&W Vertical Test Facility for SSC Collider Quadrupole Magnets
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Dixon, K. D., Billingsly, A. L., Boyes, D. W., Cantor, B. I., Hlasnicek, P., Kelley, J. P., Leamon, C. K., Maloney, J. E., Paré, G., Rey, C. M., Savignano, J. A., Stone, M. E., Whorley, D. L., and Kittel, Peter, editor
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- 1994
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17. B&W’s Magnet Test Facility for SSC Collider Quadrupole Magnets
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Kelley, J. P., Stone, M. E., Billingsly, A., Cantor, B. I., Clausen, J-J., Dixon, K., Hlasnicek, P., Kurtcuoglu, K., Löhlein, K., Maloney, J., Paré, G., Rey, C. M., Savignano, J., Schaffer, R. H., Senn, A. E., and Kittel, Peter, editor
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- 1994
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18. Control and Data Acquisition System for the B&W Vertical Dewar Facility
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Billingsly, A., Beoddy, J., Cantor, B., Hlasnicek, P., Kelley, J. P., Paré, G., Rey, C., and Nonte, John, editor
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- 1992
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19. Effets du télémonitorage dans la prise en charge du diabète
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Paré, G., Moqadem, K., Pineau, G., and St-Hilaire, C.
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- 2010
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20. The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression
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Samaan, Z, Anand, S, Zhang, X, Desai, D, Rivera, M, Pare, G, Thabane, L, Xie, C, Gerstein, H, Engert, J C, Craig, I, Cohen-Woods, S, Mohan, V, Diaz, R, Wang, X, Liu, L, Corre, T, Preisig, M, Kutalik, Z, Bergmann, S, Vollenweider, P, Waeber, G, Yusuf, S, and Meyre, D
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- 2013
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21. Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
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Surendran, P, Feofanova, EV, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, AV, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Velez Edwards, DR, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, De Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, I, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, YV, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, AI, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Davey Smith, G, Boer, RAD, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, MI, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, JI, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, Van der Harst, P, Van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, DI, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, and United Kingdom Research and Innovation
- Subjects
Genetics & Heredity ,Understanding Society Scientific Group ,Science & Technology ,business.industry ,Published Erratum ,Million Veteran Program ,MEDLINE ,Computational biology ,06 Biological Sciences ,Biology ,Blood pressure ,Text mining ,Meta-analysis ,EPIC-InterAct ,Genetics ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,business ,Life Sciences & Biomedicine ,EPIC-CVD ,11 Medical and Health Sciences ,LifeLines Cohort Study ,Developmental Biology - Abstract
In the version of this article originally published, the e-mail address of corresponding author Patricia B. Munroe was incorrect. The error has been corrected in the HTML and PDF versions of the article.
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- 2021
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22. Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis
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Ken-Dror, G, Cotlarciuc, I, Martinelli, I, Grandone, E, Hiltunen, S, Lindgren, E, Margaglione, M, Duchez, VLC, Triquenot, AB, Zedde, M, Mancuso, M, Ruigrok, YM, Marjot, T, Worrall, B, Majersik, JJ, Metso, TM, Putaala, J, Haapaniemi, E, Zuurbier, SM, Brouwer, MC, Passamonti, SM, Abbattista, M, Bucciarelli, P, Mitchell, BD, Kittner, SJ, Lemmens, R, Jern, C, Pappalardo, E, Costa, P, Colombi, M, de Sousa, DA, Rodrigues, S, Canhao, P, Tkach, A, Santacroce, R, Favuzzi, G, Arauz, A, Colaizzo, D, Spengos, K, Hodge, A, Ditta, R, Pezzini, A, Debette, S, Coutinho, JM, Thijs, V, Jood, K, Pare, G, Tatlisumak, T, Ferro, JM, Sharma, P, Ken-Dror, G, Cotlarciuc, I, Martinelli, I, Grandone, E, Hiltunen, S, Lindgren, E, Margaglione, M, Duchez, VLC, Triquenot, AB, Zedde, M, Mancuso, M, Ruigrok, YM, Marjot, T, Worrall, B, Majersik, JJ, Metso, TM, Putaala, J, Haapaniemi, E, Zuurbier, SM, Brouwer, MC, Passamonti, SM, Abbattista, M, Bucciarelli, P, Mitchell, BD, Kittner, SJ, Lemmens, R, Jern, C, Pappalardo, E, Costa, P, Colombi, M, de Sousa, DA, Rodrigues, S, Canhao, P, Tkach, A, Santacroce, R, Favuzzi, G, Arauz, A, Colaizzo, D, Spengos, K, Hodge, A, Ditta, R, Pezzini, A, Debette, S, Coutinho, JM, Thijs, V, Jood, K, Pare, G, Tatlisumak, T, Ferro, JM, and Sharma, P
- Abstract
OBJECTIVE: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. METHODS: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. RESULTS: In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10-24 ; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 × 10-16 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 × 10-16 ) increased risk of CVT compared with individuals with blood group O. INTERPRETATION: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788.
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- 2021
23. THE CLINICAL UTILITY AND ANCESTRAL DIVERSITY OF POLYGENIC RISK SCORES IN CARDIOMETABOLIC DISEASE RISK PREDICTION
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Phulka, J., Ashraf, M., Bajwa, B., Pare, G., and Laksman, Z.
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- 2023
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24. IDENTIFICATION OF PAM AS NOVEL MONOGENIC DIABETES GENE
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Feiner, J., Perrot, N., Chong, M., Lali, R., Morton, R., Mohammadi-Shemirani, P., Yusuf, S., Punthakee, Z., Gerstein, H., Pare, G., and Pigeyre, M.
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- 2023
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25. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
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Surendran, P., Feofanova, E. V., Lahrouchi, N., Ntalla, I., Karthikeyan, S., Cook, J., Chen, L., Mifsud, B., Yao, C., Kraja, A. T., Cartwright, J. H., Hellwege, J. N., Giri, A., Tragante, V., Thorleifsson, G., Liu, D. J., Prins, B. P., Stewart, I. D., Cabrera, C. P., Eales, J. M., Akbarov, A., Auer, P. L., Bielak, L. F., Bis, J. C., Braithwaite, V. S., Brody, J. A., Daw, E. W., Warren, H. R., Drenos, F., Nielsen, S. F., Faul, J. D., Fauman, E. B., Fava, C., Ferreira, T., Foley, C. N., Franceschini, N., Gao, H., Giannakopoulou, O., Giulianini, F., Gudbjartsson, D. F., Guo, X., Harris, S. E., Havulinna, A. S., Helgadottir, A., Huffman, J. E., Hwang, S. -J., Kanoni, S., Kontto, J., Larson, M. G., Li-Gao, R., Lindstrom, J., Lotta, L. A., Lu, Y., Luan, J., Mahajan, A., Malerba, G., Masca, N. G. D., Mei, H., Menni, C., Mook-Kanamori, D. O., Mosen-Ansorena, D., Muller-Nurasyid, M., Pare, G., Paul, D. S., Perola, M., Poveda, A., Rauramaa, R., Richard, M., Richardson, T. G., Sepulveda, N., Sim, X., Smith, A. V., Smith, J. A., Staley, J. R., Stanakova, A., Sulem, P., Theriault, S., Thorsteinsdottir, U., Trompet, S., Varga, T. V., Velez Edwards, D. R., Veronesi, G., Weiss, S., Willems, S. M., Yao, J., Young, R., Yu, B., Zhang, W., Zhao, J. -H., Zhao, W., Evangelou, E., Aeschbacher, S., Asllanaj, E., Blankenberg, S., Bonnycastle, L. L., Bork-Jensen, J., Brandslund, I., Braund, P. S., Burgess, S., Cho, K., Christensen, C., Connell, J., Mutsert, R., Dominiczak, A. F., Dorr, M., Eiriksdottir, G., Farmaki, A. -E., Gaziano, J. M., Grarup, N., Grove, M. L., Hallmans, G., Hansen, T., Have, C. T., Heiss, G., Jorgensen, M. E., Jousilahti, P., Kajantie, E., Kamat, M., Karajamaki, A. M., Karpe, F., Koistinen, H. A., Kovesdy, C. P., Kuulasmaa, K., Laatikainen, T., Lannfelt, L., Lee, I. -T., Lee, W. -J., de Boer, R. A., van der Harst, P., van der Meer, P., Verweij, N., Linneberg, A., Martin, L. W., Moitry, M., Nadkarni, G., Neville, M. J., Palmer, C. N. A., Papanicolaou, G. J., Pedersen, O., Peters, J., Poulter, N., Rasheed, A., Rasmussen, K. L., Rayner, N. W., Magi, R., Renstrom, F., Rettig, R., Rossouw, J., Schreiner, P. J., Sever, P. S., Sigurdsson, E. L., Skaaby, T., Sun, Y. V., Sundstrom, J., Thorgeirsson, G., Esko, T., Trabetti, E., Tsao, P. S., Tuomi, T., Turner, S. T., Tzoulaki, I., Vaartjes, I., Vergnaud, A. -C., Willer, C. J., Wilson, P. W. F., Witte, D. R., Yonova-Doing, E., Zhang, H., Aliya, N., Almgren, P., Amouyel, P., Asselbergs, F. W., Barnes, M. R., Blakemore, A. I., Boehnke, M., Bots, M. L., Bottinger, E. P., Buring, J. E., Chambers, J. C., Chen, Y. -D. I., Chowdhury, R., Conen, D., Correa, A., Davey Smith, G., Boer, R. A., Deary, I. J., Dedoussis, G., Deloukas, P., Di Angelantonio, E., Elliott, P., Butterworth, A. S., Danesh, J., Langenberg, C., Mccarthy, M. I., Franks, P. W., Rolandsson, O., Wareham, N. J., Felix, S. B., Ferrieres, J., Ford, I., Fornage, M., Franks, S., Frossard, P., Gambaro, G., Gaunt, T. R., Groop, L., Gudnason, V., Harris, T. B., Hayward, C., Hennig, B. J., Herzig, K. -H., Ingelsson, E., Tuomilehto, J., Jarvelin, M. -R., Jukema, J. W., Kardia, S. L. R., Kee, F., Kooner, J. S., Kooperberg, C., Launer, L. J., Lind, L., Loos, R. J. F., Majumder, A. S., Laakso, M., Melander, O., Mohlke, K. L., Murray, A. D., Nordestgaard, B. G., Orho-Melander, M., Packard, C. J., Padmanabhan, S., Palmas, W., Polasek, O., Porteous, D. J., Prentice, A. M., Province, M. A., Relton, C. L., Rice, K., Ridker, P. M., Rosendaal, F. R., Rotter, J. I., Rudan, I., Salomaa, V., Samani, N. J., Sattar, N., Sheu, W. H. -H., Smith, B. H., Soranzo, N., Spector, T. D., Starr, J. M., Sebert, S., Taylor, K. D., Lakka, T. A., Timpson, N. J., Tobin, M. D., Zeggini, E., Ramachandran, V. S., Virtamo, J., Volker, U., Weir, D. R., Charchar, F. J., Edwards, D. R. V., Edwards, T. L., Hung, A. M., O'Donnell, C. J., Tomaszewski, M., Caulfield, M. J., Holm, H., Lindgren, C. M., Liu, C., Manning, A. K., Morris, A. P., Morrison, A. C., Psaty, B. M., Saleheen, D., Stefansson, K., Boerwinkle, E., Chasman, D. I., Levy, D., Newton-Cheh, C., Munroe, P. B., Howson, J. M. M., Home Office, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), UNIVERSITY OF OULU, Epidemiology, Complex Disease Genetics, Research Programs Unit, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, HUS Children and Adolescents, Lastentautien yksikkö, Clinicum, Children's Hospital, Helsinki University Hospital Area, HUS Internal Medicine and Rehabilitation, Department of Medicine, Department of Biochemistry and Developmental Biology, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Endokrinologian yksikkö, Department of Public Health, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Feofanova, Elena V [0000-0003-1428-7199], Chasman, Daniel I [0000-0003-3357-0862], Munroe, Patricia B [0000-0002-4176-2947], Howson, Joanna MM [0000-0001-7618-0050], Apollo - University of Cambridge Repository, Cardiology, and ACS - Heart failure & arrhythmias
- Subjects
Candidate gene ,Blood Pressure ,GATA5 Transcription Factor ,Gene Frequency ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Hypertension ,Mutation ,Phospholipase C beta ,Polymorphism, Single Nucleotide ,LOCI ,Genome-wide association study ,0302 clinical medicine ,Polymorphism (computer science) ,genetics ,GENOME-WIDE ASSOCIATION ,MENDELIAN RANDOMIZATION ,COMMON VARIANTS ,IDENTIFIES COMMON ,RISK ,FREQUENCY ,TRAITS ,HYPERTENSION ,GENETICS ,EPIC-CVD ,11 Medical and Health Sciences ,health care economics and organizations ,Genetics & Heredity ,Genetics ,0303 health sciences ,Million Veteran Program ,1184 Genetics, developmental biology, physiology ,Single Nucleotide ,humanities ,3. Good health ,genetic association study ,EPIC-InterAct ,epidemiology ,Life Sciences & Biomedicine ,Understanding Society Scientific Group ,hypertension ,education ,Biology ,Article ,03 medical and health sciences ,Mendelian randomization ,Polymorphism ,Allele frequency ,Gene ,030304 developmental biology ,Science & Technology ,06 Biological Sciences ,meta-analysis ,Minor allele frequency ,genome-wide association studies ,3111 Biomedicine ,030217 neurology & neurosurgery ,LifeLines Cohort Study ,Developmental Biology - Abstract
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P
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- 2020
- Full Text
- View/download PDF
26. Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data
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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
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- 2020
27. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
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Surendran, P, Feofanova, E, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, A, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Edwards, DRV, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, de Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, T, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, Y, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, A, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Smith, GD, de Boer, RA, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, M, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, J, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, van der Harst, P, van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, D, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, Surendran, P, Feofanova, E, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, A, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Edwards, DRV, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, de Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, T, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, Y, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, A, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Smith, GD, de Boer, RA, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, M, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, J, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, van der Harst, P, van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, D, Levy, D, Newton-Cheh, C, Munroe, PB, and Howson, JMM
- Abstract
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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- 2020
28. Genetic risk for dengue hemorrhagic fever and dengue fever in multiple ancestries.
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Pare, G, Neupane, B, Eskandarian, S, Harris, E, Halstead, S, Gresh, L, Kuan, G, Balmaseda, A, Villar, L, Rojas, E, Osorio, JE, Anh, DD, De Silva, AD, Premawansa, S, Premawansa, G, Wijewickrama, A, Lorenzana, I, Parham, L, Rodriguez, C, Fernandez-Salas, I, Sanchez-Casas, R, Diaz-Gonzalez, EE, Saw Aye, K, May, WL, Thein, M, Bucardo, F, Reyes, Y, Blandon, P, Hirayama, K, Weiss, L, Singh, P, Newton, J, Loeb, M, Dengue Population Genetics Program, Pare, G, Neupane, B, Eskandarian, S, Harris, E, Halstead, S, Gresh, L, Kuan, G, Balmaseda, A, Villar, L, Rojas, E, Osorio, JE, Anh, DD, De Silva, AD, Premawansa, S, Premawansa, G, Wijewickrama, A, Lorenzana, I, Parham, L, Rodriguez, C, Fernandez-Salas, I, Sanchez-Casas, R, Diaz-Gonzalez, EE, Saw Aye, K, May, WL, Thein, M, Bucardo, F, Reyes, Y, Blandon, P, Hirayama, K, Weiss, L, Singh, P, Newton, J, Loeb, M, and Dengue Population Genetics Program
- Abstract
BACKGROUND: Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations. METHODS: We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls. FINDINGS: The risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other. INTERPRETATION: There is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries.
- Published
- 2020
29. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- Author
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Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Howson, J. M. (Joanna M. M.), Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), and Howson, J. M. (Joanna M. M.)
- Abstract
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 x 10(⁻⁸)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets., Correction A Publisher Correction to this article was published on 16 March 2021.
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- 2020
30. Erratum to: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (Nature Genetics, (2018), 50, 10, (1412-1425), 10.1038/s41588-018-0205-x)
- Author
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Evangelou E., Warren H. R., Mosen-Ansorena D., Mifsud B., Pazoki R., Gao H., Ntritsos G., Dimou N., Cabrera C. P., Karaman I., Ng F. L., Evangelou M., Witkowska K., Tzanis E., Hellwege J. N., Giri A., Velez Edwards D. R., Sun Y. V., Cho K., Gaziano J. M., Wilson P. W. F., Tsao P. S., Kovesdy C. P., Esko T., Magi R., Milani L., Almgren P., Boutin T., Debette S., Ding J., Giulianini F., Holliday E. G., Jackson A. U., Li-Gao R., Lin W. -Y., Luan J., Mangino M., Oldmeadow C., Prins B. P., Qian Y., Sargurupremraj M., Shah N., Surendran P., Theriault S., Verweij N., Willems S. M., Zhao J. -H., Amouyel P., Connell J., de Mutsert R., Doney A. S. F., Farrall M., Menni C., Morris A. D., Noordam R., Pare G., Poulter N. R., Shields D. C., Stanton A., Thom S., Abecasis G., Amin N., Arking D. E., Ayers K. L., Barbieri C. M., Batini C., Bis J. C., Blake T., Bochud M., Boehnke M., Boerwinkle E., Boomsma D. I., Bottinger E. P., Braund P. S., Brumat M., Campbell A., Campbell H., Chakravarti A., Chambers J. C., Chauhan G., Ciullo M., Cocca M., Collins F., Cordell H. J., Davies G., de Borst M. H., de Geus E. J., Deary I. J., Deelen J., Del Greco M F., Demirkale C. Y., Dorr M., Ehret G. B., Elosua R., Enroth S., Erzurumluoglu A. M., Ferreira T., Franberg M., Franco O. H., Gandin I., Gasparini P., Giedraitis V., Gieger C., Girotto G., Goel A., Gow A. J., Gudnason V., Guo X., Gyllensten U., Hamsten A., Harris T. B., Harris S. E., Hartman C. A., Havulinna A. S., Hicks A. A., Hofer E., Hofman A., Hottenga J. -J., Huffman J. E., Hwang S. -J., Ingelsson E., James A., Jansen R., Jarvelin M. -R., Joehanes R., Johansson A., Johnson A. D., Joshi P. K., Jousilahti P., Jukema J. W., Jula A., Kahonen M., Kathiresan S., Keavney B. D., Khaw K. -T., Knekt P., Knight J., Kolcic I., Kooner J. S., Koskinen S., Kristiansson K., Kutalik Z., Laan M., Larson M., Launer L. J., Lehne B., Lehtimaki T., Liewald D. C. M., Lin L., Lind L., Lindgren C. M., Liu Y. M., Loos R. J. F., Lopez L. M., Lu Y., Lyytikainen L. -P., Mahajan A., Mamasoula C., Marrugat J., Marten J., Milaneschi Y., Morgan A., Morris A. P., Morrison A. C., Munson P. J., Nalls M. A., Nandakumar P., Nelson C. P., Niiranen T., Nolte I. M., Nutile T., Oldehinkel A. J., Oostra B. A., O'Reilly P. F., Org E., Padmanabhan S., Palmas W., Palotie A., Pattie A., Penninx B. W. J. H., Perola M., Peters A., Polasek O., Pramstaller P. P., Nguyen Q. T., Raitakari O. T., Ren M., Rettig R., Rice K., Ridker P. M., Ried J. S., Riese H., Ripatti S., Robino A., Rose L. M., Rotter J. I., Rudan I., Ruggiero D., Saba Y., Sala C. F., Salomaa V., Samani N. J., Sarin A. -P., Schmidt R., Schmidt H., Shrine N., Siscovick D., Smith A. V., Snieder H., Sober S., Sorice R., Starr J. M., Stott D. J., Strachan D. P., Strawbridge R. J., Sundstrom J., Swertz M. A., Taylor K. D., Teumer A., Tobin M. D., Tomaszewski M., Toniolo D., Traglia M., Trompet S., Tuomilehto J., Tzourio C., Uitterlinden A. G., Vaez A., van der Most P. J., van Duijn C. M., Vergnaud A. -C., Verwoert G. C., Vitart V., Volker U., Vollenweider P., Vuckovic D., Watkins H., Wild S. H., Willemsen G., Wilson J. F., Wright A. F., Yao J., Zemunik T., Zhang W., Attia J. R., Butterworth A. S., Chasman D. I., Conen D., Cucca F., Danesh J., Hayward C., Howson J. M. M., Laakso M., Lakatta E. G., Langenberg C., Melander O., Mook-Kanamori D. O., Palmer C. N. A., Risch L., Scott R. A., Scott R. J., Sever P., Spector T. D., van der Harst P., Wareham N. J., Zeggini E., Levy D., Munroe P. B., Newton-Cheh C., Brown M. J., Metspalu A., Hung A. M., O'Donnell C. J., Edwards T. L., Psaty B. M., Tzoulaki I., Barnes M. R., Wain L. V., Elliott P., Caulfield M. J., Evangelou, E., Warren, H. R., Mosen-Ansorena, D., Mifsud, B., Pazoki, R., Gao, H., Ntritsos, G., Dimou, N., Cabrera, C. P., Karaman, I., Ng, F. L., Evangelou, M., Witkowska, K., Tzanis, E., Hellwege, J. N., Giri, A., Velez Edwards, D. R., Sun, Y. V., Cho, K., Gaziano, J. M., Wilson, P. W. F., Tsao, P. S., Kovesdy, C. P., Esko, T., Magi, R., Milani, L., Almgren, P., Boutin, T., Debette, S., Ding, J., Giulianini, F., Holliday, E. G., Jackson, A. U., Li-Gao, R., Lin, W. -Y., Luan, J., Mangino, M., Oldmeadow, C., Prins, B. P., Qian, Y., Sargurupremraj, M., Shah, N., Surendran, P., Theriault, S., Verweij, N., Willems, S. M., Zhao, J. -H., Amouyel, P., Connell, J., de Mutsert, R., Doney, A. S. F., Farrall, M., Menni, C., Morris, A. D., Noordam, R., Pare, G., Poulter, N. R., Shields, D. C., Stanton, A., Thom, S., Abecasis, G., Amin, N., Arking, D. E., Ayers, K. L., Barbieri, C. M., Batini, C., Bis, J. C., Blake, T., Bochud, M., Boehnke, M., Boerwinkle, E., Boomsma, D. I., Bottinger, E. P., Braund, P. S., Brumat, M., Campbell, A., Campbell, H., Chakravarti, A., Chambers, J. C., Chauhan, G., Ciullo, M., Cocca, M., Collins, F., Cordell, H. J., Davies, G., de Borst, M. H., de Geus, E. J., Deary, I. J., Deelen, J., Del Greco M, F., Demirkale, C. Y., Dorr, M., Ehret, G. B., Elosua, R., Enroth, S., Erzurumluoglu, A. M., Ferreira, T., Franberg, M., Franco, O. H., Gandin, I., Gasparini, P., Giedraitis, V., Gieger, C., Girotto, G., Goel, A., Gow, A. J., Gudnason, V., Guo, X., Gyllensten, U., Hamsten, A., Harris, T. B., Harris, S. E., Hartman, C. A., Havulinna, A. S., Hicks, A. A., Hofer, E., Hofman, A., Hottenga, J. -J., Huffman, J. E., Hwang, S. -J., Ingelsson, E., James, A., Jansen, R., Jarvelin, M. -R., Joehanes, R., Johansson, A., Johnson, A. D., Joshi, P. K., Jousilahti, P., Jukema, J. W., Jula, A., Kahonen, M., Kathiresan, S., Keavney, B. D., Khaw, K. -T., Knekt, P., Knight, J., Kolcic, I., Kooner, J. S., Koskinen, S., Kristiansson, K., Kutalik, Z., Laan, M., Larson, M., Launer, L. J., Lehne, B., Lehtimaki, T., Liewald, D. C. M., Lin, L., Lind, L., Lindgren, C. M., Liu, Y. M., Loos, R. J. F., Lopez, L. M., Lu, Y., Lyytikainen, L. -P., Mahajan, A., Mamasoula, C., Marrugat, J., Marten, J., Milaneschi, Y., Morgan, A., Morris, A. P., Morrison, A. C., Munson, P. J., Nalls, M. A., Nandakumar, P., Nelson, C. P., Niiranen, T., Nolte, I. M., Nutile, T., Oldehinkel, A. J., Oostra, B. A., O'Reilly, P. F., Org, E., Padmanabhan, S., Palmas, W., Palotie, A., Pattie, A., Penninx, B. W. J. H., Perola, M., Peters, A., Polasek, O., Pramstaller, P. P., Nguyen, Q. T., Raitakari, O. T., Ren, M., Rettig, R., Rice, K., Ridker, P. M., Ried, J. S., Riese, H., Ripatti, S., Robino, A., Rose, L. M., Rotter, J. I., Rudan, I., Ruggiero, D., Saba, Y., Sala, C. F., Salomaa, V., Samani, N. J., Sarin, A. -P., Schmidt, R., Schmidt, H., Shrine, N., Siscovick, D., Smith, A. V., Snieder, H., Sober, S., Sorice, R., Starr, J. M., Stott, D. J., Strachan, D. P., Strawbridge, R. J., Sundstrom, J., Swertz, M. A., Taylor, K. D., Teumer, A., Tobin, M. D., Tomaszewski, M., Toniolo, D., Traglia, M., Trompet, S., Tuomilehto, J., Tzourio, C., Uitterlinden, A. G., Vaez, A., van der Most, P. J., van Duijn, C. M., Vergnaud, A. -C., Verwoert, G. C., Vitart, V., Volker, U., Vollenweider, P., Vuckovic, D., Watkins, H., Wild, S. H., Willemsen, G., Wilson, J. F., Wright, A. F., Yao, J., Zemunik, T., Zhang, W., Attia, J. R., Butterworth, A. S., Chasman, D. I., Conen, D., Cucca, F., Danesh, J., Hayward, C., Howson, J. M. M., Laakso, M., Lakatta, E. G., Langenberg, C., Melander, O., Mook-Kanamori, D. O., Palmer, C. N. A., Risch, L., Scott, R. A., Scott, R. J., Sever, P., Spector, T. D., van der Harst, P., Wareham, N. J., Zeggini, E., Levy, D., Munroe, P. B., Newton-Cheh, C., Brown, M. J., Metspalu, A., Hung, A. M., O'Donnell, C. J., Edwards, T. L., Psaty, B. M., Tzoulaki, I., Barnes, M. R., Wain, L. V., Elliott, P., and Caulfield, M. J.
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Blood pressure ,genetic analysis - Abstract
In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
- Published
- 2018
31. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes (vol 50, pg 524, 2018)
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Malik, R, Chauhan, G, Traylor, M, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, A-K, Van der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, TM, Benavente, OR, Bevan, S, Boncoraglio, GB, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, W-M, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, DeStefano, AL, Den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, F-C, Hyacinth, IH, Ikram, MA, Ingelsson, E, Irvin, MR, Jian, X, Jimenez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, J-M, Lemmens, R, Leys, D, Lewis, CM, Lin, W-Y, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmae, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, Rothwell, PM, Rotter, JI, Rundek, T, Sacco, RL, Sakaue, S, Sale, MM, Salomaa, V, Sapkota, BR, Schmidt, R, Schmidt, CO, Schminke, U, Sharma, P, Slowik, A, Sudlow, CLM, Tanislav, C, Tatlisumak, T, Taylor, KD, Thijs, VNS, Thorleifsson, G, Thorsteinsdottir, U, Tiedt, S, Trompet, S, Tzourio, C, Van Duijn, CM, Walters, M, Wareham, NJ, Wassertheil-Smoller, S, Wilson, JG, Wiggins, KL, Yang, Q, Yusuf, S, Bis, JC, Pastinen, T, Ruusalepp, A, Schadt, EE, Koplev, S, Bjorkegren, JLM, Codoni, V, Civelek, M, Smith, NL, Tregouet, DA, Christophersen, IE, Roselli, C, Lubitz, SA, Ellinor, PT, Tai, ES, Kooner, JS, Kato, N, He, J, Van der Harst, P, Elliott, P, Chambers, JC, Takeuchi, F, Johnson, AD, Sanghera, DK, Melander, O, Jern, C, Strbian, D, Fernandez-Cadenas, I, Longstreth, WT, Rolfs, A, Hata, J, Woo, D, Rosand, J, Pare, G, Hopewell, JC, Saleheen, D, Stefansson, K, Worrall, BB, Kittner, SJ, Seshadri, S, Fornage, M, Markus, HS, Howson, JMM, Kamatani, Y, Debette, S, and Dichgans, M
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Genetics & Heredity ,International Genomics of Blood Pressure (iGEN-BP) Consortium ,COMPASS Consortium ,MEGASTROKE Consortium ,Science & Technology ,UK Young Lacunar DNA Study ,AFGen Consortium ,INVENT Consortium ,STARNET ,06 Biological Sciences ,METASTROKE Consortium ,EPIC-CVD Consortium ,BioBank Japan Cooperative Hospital Group ,International Stroke Genetics Consortium (ISGC) ,NINDS Stroke Genetics Network (SiGN) ,Neurology Working Group of the CHARGE Consortium ,EPIC-InterAct Consortium ,Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium ,Life Sciences & Biomedicine ,11 Medical and Health Sciences ,Developmental Biology - Published
- 2019
32. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events A GENIUS-CHD Study of Individual Participant Data
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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
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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.
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- 2019
33. Subsequent Event Risk in Individuals With Established Coronary Heart Disease
- Author
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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
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34. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study
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Valdes-Marquez, E, Parish, S, Clarke, R, Stari, T, Worrall, BB, Hopewell, JC, Slowik, A, Hofman, A, Algra, A, Reiner, AP, Doney, ASF, Gschwendtner, A, Ilinca, A, Giese, A-K, Lindgren, A, Vicente, AM, Norrving, B, Nordestgaard, BG, Mitchell, BD, Psaty, BM, Carty, CL, Sudlow, CLM, Anderson, C, Levi, CR, Satizabal, CL, Palmer, CNA, Gamble, DM, Woo, D, Saleheen, D, Ringelstein, EB, Valdimarsson, EM, Holliday, EG, Davies, G, Chauhan, G, Pasterkamp, G, Boncoraglio, GB, Kuhlenbaeumer, G, Thorleifsson, G, Falcone, GJ, Pare, G, Schmidt, H, Delavaran, H, Markus, HS, Aparicio, HJ, Deary, I, Cotlarciuc, I, Fernandez-Cadenas, I, Meschia, JF, Liu, J, Montaner, J, Pera, J, Cole, J, Attia, JR, Rosand, J, Ferro, JM, Bis, JC, Furie, K, Stefansson, K, Berger, K, Kostulas, K, Rannikmae, K, Ikram, MA, Benn, M, Dichgans, M, Pandolfo, M, Traylor, M, Walters, M, Sale, M, Nalls, MA, Fornage, M, van Zuydam, NR, Sharma, P, Abrantes, P, de Bakker, PIW, Higgins, P, Lichtner, P, Rothwell, PM, Amouyel, P, Yang, Q, Malik, R, Schmidt, R, Lemmens, R, van der Laan, SW, Pulit, SL, Abboud, S, Oliveira, SA, Gretarsdottir, S, Debette, S, Williams, SR, Bevan, S, Kittner, SJ, Seshadri, S, Mosley, T, Battey, TWK, Tatlisumak, T, Thorsteinsdottir, U, Thijs, VNS, Longstreth, WT, Zhao, W, Chen, W-M, Cheng, Y-C, Valdes-Marquez, E, Parish, S, Clarke, R, Stari, T, Worrall, BB, Hopewell, JC, Slowik, A, Hofman, A, Algra, A, Reiner, AP, Doney, ASF, Gschwendtner, A, Ilinca, A, Giese, A-K, Lindgren, A, Vicente, AM, Norrving, B, Nordestgaard, BG, Mitchell, BD, Psaty, BM, Carty, CL, Sudlow, CLM, Anderson, C, Levi, CR, Satizabal, CL, Palmer, CNA, Gamble, DM, Woo, D, Saleheen, D, Ringelstein, EB, Valdimarsson, EM, Holliday, EG, Davies, G, Chauhan, G, Pasterkamp, G, Boncoraglio, GB, Kuhlenbaeumer, G, Thorleifsson, G, Falcone, GJ, Pare, G, Schmidt, H, Delavaran, H, Markus, HS, Aparicio, HJ, Deary, I, Cotlarciuc, I, Fernandez-Cadenas, I, Meschia, JF, Liu, J, Montaner, J, Pera, J, Cole, J, Attia, JR, Rosand, J, Ferro, JM, Bis, JC, Furie, K, Stefansson, K, Berger, K, Kostulas, K, Rannikmae, K, Ikram, MA, Benn, M, Dichgans, M, Pandolfo, M, Traylor, M, Walters, M, Sale, M, Nalls, MA, Fornage, M, van Zuydam, NR, Sharma, P, Abrantes, P, de Bakker, PIW, Higgins, P, Lichtner, P, Rothwell, PM, Amouyel, P, Yang, Q, Malik, R, Schmidt, R, Lemmens, R, van der Laan, SW, Pulit, SL, Abboud, S, Oliveira, SA, Gretarsdottir, S, Debette, S, Williams, SR, Bevan, S, Kittner, SJ, Seshadri, S, Mosley, T, Battey, TWK, Tatlisumak, T, Thorsteinsdottir, U, Thijs, VNS, Longstreth, WT, Zhao, W, Chen, W-M, and Cheng, Y-C
- Abstract
OBJECTIVE: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. METHODS: We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. RESULTS: A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10-8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10-3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10-3) when compared with that for CHD. CONCLUSIONS: In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
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35. Proceedings of the Canadian Frailty Network Workshop: Identifying Biomarkers of Frailty to Support Frailty Risk Assessment, Diagnosis and Prognosis. Toronto, January 15, 2018
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Muscedere, J., Kim, P. M., Afilalo, J., Balion, C., Baracos, V. E., Bowdish, D., Cesari, M., Erusalimsky, J. D., Fulop, T., Heckman, G., Howlett, S. E., Khadaroo, R. G., Kirkland, J. L., Rodriguez Manas, L., Marzetti, Emanuele, Pare, G., Raina, P., Rockwood, K., Sinclair, A., Skappak, C., Verschoor, C., Walter, S., Marzetti E. (ORCID:0000-0001-9567-6983), Muscedere, J., Kim, P. M., Afilalo, J., Balion, C., Baracos, V. E., Bowdish, D., Cesari, M., Erusalimsky, J. D., Fulop, T., Heckman, G., Howlett, S. E., Khadaroo, R. G., Kirkland, J. L., Rodriguez Manas, L., Marzetti, Emanuele, Pare, G., Raina, P., Rockwood, K., Sinclair, A., Skappak, C., Verschoor, C., Walter, S., and Marzetti E. (ORCID:0000-0001-9567-6983)
- Abstract
The Canadian Frailty Network (CFN), a pan-Canadian not-for-profit organization funded by the Government of Canada through the Networks of Centres of Excellence Program, is dedicated to improving the care of older Canadians living with frailty. The CFN has partnered with the Canadian Longitudinal Study on Aging (CLSA) to measure potential frailty biomarkers in biological samples (whole blood, plasma, urine) collected in over 30,000 CLSA participants. CFN hosted a workshop in Toronto on January 15 2018, bringing together experts in the field of biomarkers, aging and frailty. The overall objectives of the workshop were to start building a consensus on potential frailty biomarker domains and identify specific frailty biomarkers to be measured in the CLSA biological samples. The workshop was structured with presentations in the morning to frame the discussions for the afternoon session, which was organized as a free-flowing discussion to benefit from the expertise of the participants. Participants and speakers were from Canada, Italy, Spain, United Kingdom and the United States. Herein we provide pertinent background information, a summary of all the presentations with key figures and tables, and the distillation of the discussions. In addition, moving forward, the principles CFN will use to approach frailty biomarker research and development are outlined. Findings from the workshop are helping CFN and CLSA plan and conduct the analysis of biomarkers in the CLSA samples and which will inform a follow-up data access competition.
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36. Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
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Marini, S, Crawford, K, Morotti, A, Lee, MJ, Pezzini, A, Moomaw, CJ, Flaherty, ML, Montaner, J, Roquer, J, Jimenez-Conde, J, Giralt-Steinhauer, E, Elosua, R, Cuadrado-Godia, E, Soriano-Tarraga, C, Slowik, A, Jagiella, JM, Pera, J, Urbanik, A, Pichler, A, Hansen, BM, McCauley, JL, Tirschwell, DL, Selim, M, Brown, DL, Silliman, SL, Worrall, BB, Meschia, JF, Kidwell, CS, Testai, FD, Kittner, SJ, Schmidt, H, Enzinger, C, Deary, LJ, Rannikmae, K, Samarasekera, N, Salman, RA-S, Sudlow, CL, Klijn, CJM, van Nieuwenhuizen, KM, Fernandez-Cadenas, I, Delgado, P, Nonving, B, Lindgren, A, Goldstein, JN, Viswanathan, A, Greenberg, SM, Falcone, GJ, Biffi, A, Langefeld, CD, Woo, D, Rosand, J, Anderson, CD, Smoller, S, Sorkin, J, Wang, X, Pikula, A, Wolf, P, Debette, S, Seshadri, S, de Bakker, P, Chasman, D, Rexrode, K, Chen, I, Rotter, J, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Cotlarcius, L, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lennnnens, R, Ahmadi, K, Opherk, C, Duering, M, Dichgans, M, Malik, R, Gonik, M, Staals, J, Melander, O, Burri, P, Sadr-Nabavi, A, Romero, J, Anderson, C, Falcone, G, Brouwers, B, Rost, N, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pare, G, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jem, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Hansen, B, Norrving, B, Smith, G, Martin, JJ, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Hunter, J, Attia, J, Farrall, M, Giese, A-K, Fomage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, Sheth, K, Marini, S, Crawford, K, Morotti, A, Lee, MJ, Pezzini, A, Moomaw, CJ, Flaherty, ML, Montaner, J, Roquer, J, Jimenez-Conde, J, Giralt-Steinhauer, E, Elosua, R, Cuadrado-Godia, E, Soriano-Tarraga, C, Slowik, A, Jagiella, JM, Pera, J, Urbanik, A, Pichler, A, Hansen, BM, McCauley, JL, Tirschwell, DL, Selim, M, Brown, DL, Silliman, SL, Worrall, BB, Meschia, JF, Kidwell, CS, Testai, FD, Kittner, SJ, Schmidt, H, Enzinger, C, Deary, LJ, Rannikmae, K, Samarasekera, N, Salman, RA-S, Sudlow, CL, Klijn, CJM, van Nieuwenhuizen, KM, Fernandez-Cadenas, I, Delgado, P, Nonving, B, Lindgren, A, Goldstein, JN, Viswanathan, A, Greenberg, SM, Falcone, GJ, Biffi, A, Langefeld, CD, Woo, D, Rosand, J, Anderson, CD, Smoller, S, Sorkin, J, Wang, X, Pikula, A, Wolf, P, Debette, S, Seshadri, S, de Bakker, P, Chasman, D, Rexrode, K, Chen, I, Rotter, J, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Cotlarcius, L, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lennnnens, R, Ahmadi, K, Opherk, C, Duering, M, Dichgans, M, Malik, R, Gonik, M, Staals, J, Melander, O, Burri, P, Sadr-Nabavi, A, Romero, J, Anderson, C, Falcone, G, Brouwers, B, Rost, N, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pare, G, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jem, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Hansen, B, Norrving, B, Smith, G, Martin, JJ, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Hunter, J, Attia, J, Farrall, M, Giese, A-K, Fomage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, and Sheth, K
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37. Reproducibility of Computer-Quantified Carotid Plaque Echogenicity: Can We Overcome the Subjectivity?
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Sabetai, M. M., Tegos, T. J., Nicolaides, A. N., Dhanjil, S., Pare, G. J., and Stevens, J. M.
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- 2000
38. Plaque echodensity and not per cent stenosis predicts the presence of ipsilateral silent brain infarcts in patients with asymptomatic carotid stenosis
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Sabetai, M. M., Tegos, T. J., Dhanjil, S., Elatrozy, T. S., Pare, G., Stevens, J., and Nicolaides, A. N.
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- 1999
39. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)
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Evangelou, E, Warren, HR, Mosen-Ansorena, D, Mifsud, B, Pazoki, R, Gao, H, Ntritsos, G, Dimou, N, Cabrera, CP, Karaman, I, Fu, LN, Evangelou, M, Witkowska, K, Tzanis, E, Hellwege, JN, Giri, A, Edwards, DRV, Sun, YV, Cho, K, Gaziano, JM, Wilson, PWF, Tsao, PS, Kovesdy, CP, Esko, T, Magi, R, Milani, L, Almgren, P, Boutin, T, Debette, S, Ding, J, Giulianini, F, Holliday, EG, Jackson, AU, Li-Gao, R, Lin, W-Y, Luan, J, Mangino, M, Oldmeadow, C, Prins, BP, Qian, Y, Sargurupremraj, M, Shah, N, Surendran, P, Theriault, S, Verweij, N, Willems, SM, Zhao, J-H, Amouyel, P, Connell, J, De Mutsert, R, Doney, ASF, Farrall, M, Menni, C, Morris, AD, Noordam, R, Pare, G, Poulter, NR, Shields, DC, Stanton, A, Thom, S, Abecasis, G, Amin, N, Arking, DE, Ayers, KL, Barbieri, CM, Batini, C, Bis, JC, Blake, T, Bochud, M, Boehnke, M, Boerwinkle, E, Boomsma, DI, Bottinger, EP, Braund, PS, Brumat, M, Campbell, A, Campbell, H, Chakravarti, A, Chambers, JC, Chauhan, G, Ciullo, M, Cocca, M, Collins, F, Cordell, HJ, Davies, G, De Borst, MH, De Geus, EJ, Deary, IJ, Deelen, J, Del Greco, FM, Demirkale, CY, Dorr, M, Ehret, GB, Elosua, R, Enroth, S, Erzurumluoglu, AM, Ferreira, T, Franberg, M, Franco, OH, Gandin, I, Gasparini, P, Giedraitis, V, Gieger, C, Girotto, G, Goel, A, Gow, AJ, Gudnason, V, Guo, X, Gyllensten, U, Hamsten, A, Harris, TB, Harris, SE, Hartman, CA, Havulinna, AS, Hicks, AA, Hofer, E, Hofman, A, Hottenga, J-J, Huffman, JE, Hwang, S-J, Ingelsson, E, James, A, Jansen, R, Jarvelin, M-R, Joehanes, R, Johansson, A, Johnson, AD, Joshi, PK, Jousilahti, P, Jukema, JW, Jula, A, Kahonen, M, Kathiresan, S, Keavney, BD, Khaw, K-T, Knekt, P, Knight, J, Kolcic, I, Kooner, JS, Koskinen, S, Kristiansson, K, Kutalik, Z, Laan, M, Larson, M, Launer, LJ, Lehne, B, Lehtimaki, T, Liewald, DCM, Lin, L, Lind, L, Lindgren, CM, Liu, Y, Loos, RJF, Lopez, LM, Lu, Y, Lyytikainen, L-P, Mahajan, A, Mamasoula, C, Marrugat, J, Marten, J, Milaneschi, Y, Morgan, A, Morris, AP, Morrison, AC, Munson, PJ, Nalls, MA, Nandakumar, P, Nelson, CP, Niiranen, T, Nolte, IM, Nutile, T, Oldehinkel, AJ, Oostra, BA, O'Reilly, PF, Org, E, Padmanabhan, S, Palmas, W, Palotie, A, Pattie, A, Penninx, BWJH, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Quang, TN, Raitakari, OT, Ren, M, Rettig, R, Rice, K, Ridker, PM, Ried, JS, Riese, H, Ripatti, S, Robino, A, Rose, LM, Rotter, JI, Rudan, I, Ruggiero, D, Saba, Y, Sala, CF, Salomaa, V, Samani, NJ, Sarin, A-P, Schmidt, R, Schmidt, H, Shrine, N, Siscovick, D, Smith, AV, Snieder, H, Sober, S, Sorice, R, Starr, JM, Stott, DJ, Strachan, DP, Strawbridge, RJ, Sundstrom, J, Swertz, MA, Taylor, KD, Teumer, A, Tobin, MD, Tomaszewski, M, Toniolo, D, Traglia, M, Trompet, S, Tuomilehto, J, Tzourio, C, Uitterlinden, AG, Vaez, A, Van der Most, PJ, Van Duijn, CM, Vergnaud, A-C, Verwoert, GC, Vitart, V, Volker, U, Vollenweider, P, Vuckovic, D, Watkins, H, Wild, SH, Willemsen, G, Wilson, JF, Wright, AF, Yao, J, Zemunik, T, Zhang, W, Attia, JR, Butterworth, AS, Chasman, DI, Conen, D, Cucca, F, Danesh, J, Hayward, C, Howson, JMM, Laakso, M, Lakatta, EG, Langenberg, C, Melander, O, Mook-Kanamori, DO, Palmer, CNA, Risch, L, Scott, RA, Scott, RJ, Sever, P, Spector, TD, Van der Harst, P, Wareham, NJ, Zeggini, E, Levy, D, Munroe, PB, Newton-Cheh, C, Brown, MJ, Metspalu, A, Hung, AM, O'Donnell, CJ, Edwards, TL, Psaty, BM, Tzoulaki, I, Barnes, MR, Wain, LV, Elliott, P, and Caulfield, MJ
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Genetics & Heredity ,Science & Technology ,Million Veteran Program ,06 Biological Sciences ,Life Sciences & Biomedicine ,11 Medical and Health Sciences ,Developmental Biology - Abstract
Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0205-x, published online 17 September 2018.
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- 2018
40. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits
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EVANGELOU, E., WARREN, H. R., MOSEN-ANSORENA, D., MIFSUD, B., PAZOKI, R., Gao, H., NTRITSOS, G., DIMOU, N., CABRERA, C. P., Karaman, I., NG, F. L., Evangelou, M., WITKOWSKA, K., TZANIS, E., HELLWEGE, J. N., Giri, A., VELEZ EDWARDS, D. R., Sun, Y. V., Cho, K., GAZIANO, J. M., WILSON, P. W. F., TSAO, P. S., Kovesdy, C. P., ESKO, T., MAGI, R., Milani, L., Almgren, P., Boutin, T., Debette, Stéphanie, Ding, J., GIULIANINI, F., HOLLIDAY, E. G., JACKSON, A. U., LI-GAO, R., LIN, W. Y., Luan, J., Mangino, M., OLDMEADOW, C., PRINS, B. P., Qian, Y., Sargurupremraj, Muralidharan, Shah, N., SURENDRAN, P., THERIAULT, S., VERWEIJ, N., WILLEMS, S. M., Zhao, J. H., Amouyel, P., Connell, J., DE MUTSERT, R., DONEY, A. S. F., Farrall, M., MENNI, C., NOORDAM, R., Pare, G., POULTER, N. R., SHIELDS, D. C., STANTON, A., THOM, S., ABECASIS, G., Amin, N., ARKING, D. E., Ayers, K. L., BARBIERI, C. M., Batini, C., BIS, J. C., Blake, T., Bochud, M., Boehnke, M., BOERWINKLE, E., Boomsma, D. I., BOTTINGER, E. P., BRAUND, P. S., BRUMAT, M., Campbell, A., Campbell, H., Chakravarti, A., CHAMBERS, J. C., Chauhan, Ganesh, Ciullo, M., COCCA, M., Collins, F., CORDELL, H. J., Davies, G., DE BORST, M. H., DE GEUS, E. J., DEARY, I. J., DEELEN, J., DEL GRECO, M. F., DEMIRKALE, C. Y., DORR, M., EHRET, G. B., ELOSUA, R., ENROTH, S., ERZURUMLUOGLU, A. M., Ferreira, T., Franberg, M., FRANCO, O. H., GANDIN, I., Gasparini, P., GIEDRAITIS, V., Gieger, C., GIROTTO, G., Goel, A., GOW, A. J., GUDNASON, V., Guo, X., GYLLENSTEN, U., HAMSTEN, A., HARRIS, T. B., Harris, S. E., HARTMAN, C. A., HAVULINNA, A. S., HICKS, A. A., Hofer, E., Hofman, A., HOTTENGA, J. J., HUFFMAN, J. E., Hwang, S. J., INGELSSON, E., James, A., Jansen, R., JARVELIN, M. R., JOEHANES, R., Johansson, A., JOHNSON, A. D., Joshi, P. K., JOUSILAHTI, P., JUKEMA, J. W., JULA, A., KAHONEN, M., KATHIRESAN, S., KEAVNEY, B. D., Khaw, K. T., KNEKT, P., Knight, J., KOLCIC, I., KOONER, J. S., KOSKINEN, S., KRISTIANSSON, K., KUTALIK, Z., Laan, M., Larson, M., LAUNER, L. J., LEHNE, B., LEHTIMAKI, T., LIEWALD, D. C. M., Lin, L., LIND, L., LINDGREN, C. M., Liu, Y., LOOS, R. J. F., LOPEZ, L. M., Lu, Y., LYYTIKAINEN, L. P., Mahajan, A., MAMASOULA, C., MARRUGAT, J., MARTEN, J., MILANESCHI, Y., Morgan, A., MORRIS, A. D., MORRISON, A. C., MUNSON, P. J., Nalls, M. A., NANDAKUMAR, P., NELSON, C. P., NIIRANEN, T., Nolte, I. M., Nutile, T., Oldehinkel, A. J., Oostra, B. A., O'REILLY, P. F., ORG, E., PADMANABHAN, S., PALMAS, W., Palotie, A., PATTIE, A., PENNINX, Bwjh, Perola, M., Peters, A., POLASEK, O., PRAMSTALLER, P. P., Nguyen, Q. T., RAITAKARI, O. T., REN, M., Rettig, R., Rice, K., RIDKER, P. M., RIED, J. S., RIESE, H., RIPATTI, S., ROBINO, A., ROSE, L. M., ROTTER, J. I., RUDAN, I., Ruggiero, D., SABA, Y., SALA, C. F., SALOMAA, V., SAMANI, N. J., SARIN, A. P., Schmidt, R., Schmidt, H., SHRINE, N., SISCOVICK, D., SMITH, A. V., SNIEDER, H., SOBER, S., Sorice, R., STARR, J. M., STOTT, D. J., Strachan, D. P., STRAWBRIDGE, R. J., SUNDSTROM, J., SWERTZ, M. A., TAYLOR, K. D., TEUMER, A., TOBIN, M. D., TOMASZEWSKI, M., TONIOLO, D., TRAGLIA, M., TROMPET, S., TUOMILEHTO, J., Tzourio, Christophe, UITTERLINDEN, A. G., VAEZ, A., VAN DER MOST, P. J., VAN DUIJN, C. M., VERGNAUD, A. C., VERWOERT, G. C., Vitart, V., VOLKER, U., Vollenweider, P., VUCKOVIC, D., WATKINS, H., WILD, S. H., Willemsen, G., WILSON, J. F., WRIGHT, A. F., Yao, J., ZEMUNIK, T., Zhang, W., ATTIA, J. R., BUTTERWORTH, A. S., Chasman, D. I., CONEN, D., Cucca, F., DANESH, J., Hayward, C., HOWSON, J. M. M., Laakso, M., LAKATTA, E. G., Langenberg, C., MELANDER, O., MOOK-KANAMORI, D. O., PALMER, C. N. A., Risch, L., SCOTT, R. A., SEVER, P., SPECTOR, T. D., Van Der Harst, P., Wareham, N. J., Zeggini, E., Levy, D., MUNROE, P. B., NEWTON-CHEH, C., Brown, M. J., Metspalu, A., HUNG, A. M., O'DONNELL, C. J., EDWARDS, T. L., PSATY, B. M., TZOULAKI, I., BARNES, M. R., WAIN, L. V., Elliott, P., CAULFIELD, M. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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VINTAGE ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,HEALTHY - Abstract
In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
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- 2018
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- View/download PDF
41. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
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Hart, RG, Sharma, M, Mundl, H, Kasner, SE, Bangdiwala, SI, Berkowitz, SD, Swaminathan, B, Lavados, P, Wang, Y, Davalos, A, Shamalov, N, Mikulik, R, Cunha, L, Lindgren, A, Arauz, A, Lang, W, Czlonkowska, A, Eckstein, J, Gagliardi, RJ, Amarenco, P, Ameriso, SF, Tatlisumak, T, Veltkamp, R, Hankey, GJ, Toni, D, Bereczki, D, Uchiyama, S, Ntaios, G, Yoon, BW, Brouns, R, Endres, M, Muir, KW, Bornstein, N, Ozturk, S, O'Donnell, MJ, Basson, MMD, Pare, G, Pater, C, Kirsch, B, Sheridan, P, Peters, G, Weitz, JI, Peacock, WF, Shoamanesh, A, Benavente, OR, Joyner, C, Themeles, E, and Connolly, SJ
- Abstract
BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P
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- 2018
42. Erratum to: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits
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Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), Caulfield, M. (Mark), Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), and Caulfield, M. (Mark)
- Abstract
In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
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43. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
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Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), Morris, R.W. (Richard), Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), and Morris, R.W. (Richard)
- Abstract
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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- 2018
- Full Text
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44. BAFopathies' DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes
- Author
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Aref-Eshghi, E, Bend, EG, Hood, RL, Schenkel, LC, Carere, DA, Chakrabarti, R, Nagamani, SCS, Cheung, SW, Campeau, PM, Prasad, C, Siu, VM, Brady, L, Tarnopolsky, MA, Callen, DJ, Innes, AM, White, SM, Meschino, WS, Shuen, AY, Pare, G, Bulman, DE, Ainsworth, PJ, Lin, H, Rodenhiser, DI, Hennekam, RC, Boycott, KM, Schwartz, CE, Sadikovic, B, Aref-Eshghi, E, Bend, EG, Hood, RL, Schenkel, LC, Carere, DA, Chakrabarti, R, Nagamani, SCS, Cheung, SW, Campeau, PM, Prasad, C, Siu, VM, Brady, L, Tarnopolsky, MA, Callen, DJ, Innes, AM, White, SM, Meschino, WS, Shuen, AY, Pare, G, Bulman, DE, Ainsworth, PJ, Lin, H, Rodenhiser, DI, Hennekam, RC, Boycott, KM, Schwartz, CE, and Sadikovic, B
- Abstract
Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening.
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- 2018
45. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
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Pulit, SL, Weng, L-C, McArdle, PF, Trinquart, L, Choi, SH, Mitchell, BD, Rosand, J, de Bakker, PIW, Benjamin, EJ, Ellinor, PT, Kittner, SJ, Lubitz, SA, Anderson, CD, Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, A, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Mueller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Doerr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikainen, L-P, Seppala, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Theriault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Clauss, S, Deo, R, Rader, DJ, Shah, S, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Pare, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, Shoemaker, MB, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kahonen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, Y-DI, Sandhu, RK, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Voelker, U, Joeckel, K-H, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, van der Harst, P, Lokki, M-L, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, J, Maerz, W, Lehtimaki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kaeaeb, S, Chasman, D, Heckbert, SR, Tanaka, T, Lunetta, KL, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Seshadri, S, de Bakker, P, Rexrode, K, Chen, I, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez-Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lemmens, R, Ahmadi, K, Opherk, C, Duering, M, Gonik, M, Staals, J, Burri, P, Sadr-Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Jose Martin, J, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, A, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Rannikmae, K, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, A-K, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez-Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, Sheth, K, Pulit, SL, Weng, L-C, McArdle, PF, Trinquart, L, Choi, SH, Mitchell, BD, Rosand, J, de Bakker, PIW, Benjamin, EJ, Ellinor, PT, Kittner, SJ, Lubitz, SA, Anderson, CD, Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, A, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Mueller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Doerr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikainen, L-P, Seppala, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Theriault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Clauss, S, Deo, R, Rader, DJ, Shah, S, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Pare, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, Shoemaker, MB, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kahonen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, Y-DI, Sandhu, RK, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Voelker, U, Joeckel, K-H, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, van der Harst, P, Lokki, M-L, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, J, Maerz, W, Lehtimaki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kaeaeb, S, Chasman, D, Heckbert, SR, Tanaka, T, Lunetta, KL, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Seshadri, S, de Bakker, P, Rexrode, K, Chen, I, Luke, M, Sale, M, Lee, T-H, Chang, K-C, Elkind, M, Goldstein, L, James, ML, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez-Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lemmens, R, Ahmadi, K, Opherk, C, Duering, M, Gonik, M, Staals, J, Burri, P, Sadr-Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, Y-FY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Jose Martin, J, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, A, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Rannikmae, K, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, Y-C, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, A-K, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez-Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, J-M, and Sheth, K
- Abstract
OBJECTIVE: We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. METHODS: We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. RESULTS: We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10-4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 × 10-48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1). CONCLUSIONS: Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
- Published
- 2018
46. Genetic studies of body mass index yield new insights for obesity biology
- Author
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J., Peltonen L., Vartiainen E., Brand S. M., Staessen J. A., Wang T. J., Burton P. R., Artigas M. S., Dong Y., Wang X., Zhu H., Rudock M. E., Heckbert S. R., Smith N. L., Wiggins K. L., Doumatey A., Shriner D., Veldre G., Viigimaa M., Kinra S., Prabhakaran D., Tripathy V., Langefeld C. D., Rosengren A., Thelle D. S., Corsi A. M., Singleton A., Hilton G., Salako T., Iwai N., Kita Y., Ogihara T., Ohkubo T., Okamura T., Ueshima H., Umemura S., Eyheramendy S., Meitinger T., Cho Y. S., Kim H. L., Scott J., Sehmi J. S., Hedblad B., Nilsson P., Smith G. D., Raffel L. J., Yao J., Schwartz S. M., Ikram M., W L., Mosley T. H., Seshadri S., Shrine N. R., Wain L. V., Zitting P., Cooper J. A., van Gilst W. H., Janipalli C. S., Mani K., Yajnik C. S., Mattace-Raso F. U., Lakatta E. G., Orru M., Scuteri A., Ala-Korpela M., Kangas A. J., Soininen P., Tukiainen T., Wurtz P., Ong R. T., Dorr M., Galan P., Hercberg S., Lathrop M., Zelenika D., Zhai G., Meschia J. F., Sharma P., Terzic J., Kumar M., Denniff M., Zukowska-Szczechowska E., Wagenknecht L. E., Fowkes F., Charchar F. J., Guo X., Rotimi C., Bots M. L., Brand E., Talmud P. J., Nyberg F., Laan M., Palmer L. J., van der Schouw Y. T., Casas J. P., Vineis P., Ganesh S. K., Wong T. Y., Tai E. S., Morris R. W., Marmot M. G., Miki T., Chandak G. R., Zhu X., Elosua R., Soranzo N., Sijbrands E. J., Uda M., Vasan R. S., Alizadeh B. Z., de Boer R. A., Boezen H. M., Hillege H. L., van der Klauw M. M., Ormel J., Rosmalen J. G., Slaets J. P., Lagou V., Welch R. P., Wheeler E., Rehnberg E., Rasmussen-Torvik L. J., Lecoeur C., Johnson P. C., Sennblad B., Salo P., Timpson N. J., Evans D. M., St Pourcain B., Bielak L. F., Horikoshi M., Navarro P., Raychaudhuri S., Chen H., Rybin D., Willems S. M., Song K., An P., Marullo L., Jansen H., Pankow J. S., Edkins S., Varga T. V., Oksa H., Antonella M., Kong A., Herder C., Antti J., Small K., Miljkovic I., Atalay M., Kiess W., Smit J. H., Campbell S., Fowkes G. R., Rathmann W., Maerz W., Watanabe R. M., de Geus E. J., Penninx B. W., Toenjes A., Peyser P. A., Korner A., Dupuis J., Cucca F., Balkau B., Bouatia-Naji N., Purcell S., Musunuru K., Ardissino D., Mannucci P. M., Anand S., Engert J. C., Morgan T., Spertus J. A., Stoll M., Girelli D., McKeown P. P., Patterson C. C., Merlini P. A., Berzuini C., Bernardinelli L., Peyvandi F., Tubaro M., Celli P., Fetiveau R., Marziliano N., Casari G., Galli M., Ribichini F., Rossi M., Bernardi F., Zonzin P., Piazza A., Yee J., Friedlander Y., Marrugat J., Subirana I., Sala J., Ramos R., Williams G., Nathan D. M., Macrae C. A., Berglund G., Asselta R., Duga S., Spreafico M., Daly M. J., Nemesh J., Korn J. M., Surti A., Gianniny L., Parkin M., Burtt N., Gabriel S. B., Wright B. J., Ball S. G., Schunkert I., Linsel-Nitschke P., Lieb W., Fischer M., Grosshennig A., Preuss M., Scholz M., Chen Z., Wilensky R., Matthai W., Qasim A., Hakonarson H. H., Devaney J., Pichard A. D., Kent K. M., Satler L., Lindsay J. M., Waksman R., Knouff C. W., Scheffold T., Berger K., Huge A., Martinelli N., Olivieri O., Corrocher R., Xie C., Ahmadi K. R., Ainali C., Bataille V., Bell J. T., Buil A., Dermitzakis E. T., Dimas A. S., Durbin R., Glass D., Hassanali N., Ingle C., Knowles D., Krestyaninova M., Lowe C. E., Meduri E., Di Meglio P., Montgomery S. B., Nestle F. O., Nica A. C., Nisbet J., O'rahilly S., Parts L., Potter S., Sekowska M., Shin S. Y., Surdulescu G., Travers M. E., Tsaprouni L., Tsoka S., Wilk A., Yang T. P., Higashio J., Williams R., Nato A., Ambite J. L., Deelman E., Manolio T., Heiss G., Taylor K., Avery C., Graff M., Lin D., Quibrera M., Cochran B., Kao L., Umans J., Cole S., Maccluer J., Person S., Gross M., Fornage M., Durda P., Jenny N., Patsy B., Arnold A., Buzkova P., Haines J., Murdock D., Glenn K., Brown-Gentry K., Thornton-Wells T., Dumitrescu L., Bush W. S., Mitchell S. L., Goodloe R., Wilson S., Boston J., Malinowski J., Restrepo N., Oetjens M., Fowke J., Spencer K., Pendergrass S., Le Marchand L., Park L., Tiirikainen M., Kolonel L., Cheng I., Wang H., Shohet R., Stram D., Henderson B., Monroe K., Anderson G., Carlson C., Prentice R., Lacroix A., Wu C., Carty C., Rosse S., Young A., Kocarnik J., Lin Y., Jackson R., Duggan D., Kuller L., He C., Sulem P., Barbalic M., Broer L., Byrne E. M., Gudbjartsson D. F., McArdle P. F., Porcu E., van Wingerden S. W., Zhuang W. V., Lauc L. B., Broekmans F. J., Burri A., Chen C., Corre T., Coviello A. D., D'adamo P., Davies G., Deary I. J., Ebrahim S., Fauser B. C., Ferreli L., Folsom A. R., Hankinson S. E., Hass M., Janssens A. C., Karasik D., Keyzer J., Kiel D. P., Lahti J., Lai S., Laisk T., Laven J. S., Liu J., Lopez L. M., Louwers Y. V., Marongiu M., Klaric I. M., Masciullo C., Melzer D., Newman A. B., Pare G., Peeters P. H., Pop V. J., Raikkonen K., Salumets A., Stacey S. N., Starr J. M., Stathopoulou M. G., Styrkarsdottir U., Tenesa A., Tryggvadottir L., Tsui K., van Dam R. M., van Gils C. H., van Nierop P., Vink J. M., Voorhuis M., Widen E., Wijnands-Van Gent C. J., Yerges-Armstrong L. M., Zgaga L., Zygmunt M., Buring J. E., Crisponi L., Demerath E. W., Streeten E. A., Murray A., Visser J. A., Lunetta K. L., Elks C. E., Cousminer D. L., Koller D. L., Lin P., Smith E. N., Warrington N. M., Alavere H., Berenson G. S., Blackburn H., Busonero F., Chen W., Couper D., Easton D. F., Eriksson J., Foroud T., Kilpelainen T. O., Li S., Murray S. S., Ness A. R., Northstone K., Peacock M., Pennell C. E., Pharoah P., Rafnar T., Rice J. P., Ring S. M., Schork N. J., Segre A. V., Sovio U., Srinivasan S. R., Tammesoo M. L., van Meurs J. B., Young L., Bierut L. J., and Econs M. J.
- Abstract
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
- Published
- 2015
47. Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
- Author
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Zhao, W., Rasheed, A., Tikkanen, E., Lee, J.J., Butterworth, A.S., Howson, J.M.M., Assimes, T.L., Chowdhury, R., Orho-Melander, M., Damrauer, S., Small, A., Asma, S., Imamura, M., Yamauch, T., Chambers, J.C., Chen, P., Sapkota, B.R., Shah, N., Jabeen, S., Surendran, P., Lu, Y.C., Zhang, W.H., Imran, A., Abbas, S., Majeed, F., Trindade, K., Qamar, N., Mallick, N.H., Yaqoob, Z., Saghir, T., Rizvi, S.N.H., Memon, A., Rasheed, S.Z., Memon, F.U.R., Mehmood, K., Ahmed, N., Qureshi, I.H., Tanveer-us-Salam, Iqbal, W., Malik, U., Mehra, N., Kuo, J.Z., Sheu, W.H.H., Guo, X.Q., Hsiung, C.A., Juang, J.M.J., Taylor, K.D., Hung, Y.J., Lee, W.J., Quertermous, T., Lee, I.T., Hsu, C.C., Bottinger, E.P., Ralhan, S., Teo, Y.Y., Wang, T.D., Alam, D.S., Angelantonio, E. di, Epstein, S., Nielsen, S.F., Nordestgaard, B.G., Tybjaerg-Hansen, A., Young, R., Benn, M., Frikke-Schmidt, R., Kamstrup, P.R., Biobank, M., Jukema, J.W., Sattar, N., Smit, R., Chung, R.H., Liang, K.W., Anand, S., Sanghera, D.K., Ripatti, S., Loos, R.J.F., Kooner, J.S., Tai, E.S., Rotter, J.I., Chen, Y.D.I., Frossard, P., Maeda, S., Kadowaki, T., Reilly, M., Pare, G., Melander, O., Salomaa, V., Rader, D.J., Danesh, J., Voight, B.F., Saleheen, D., CHD Exome Consortium, EPIC-CVD Consortium, EPIC-Interact Consortium, Butterworth, Adam [0000-0002-6915-9015], Howson, Joanna [0000-0001-7618-0050], Chowdhury, Rajiv [0000-0003-4881-5690], Surendran, Praveen [0000-0002-4911-6077], Di Angelantonio, Emanuele [0000-0001-8776-6719], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,endocrine system diseases ,EPIC-Interact Consortium ,Genome-wide association study ,Coronary Disease ,Type 2 diabetes ,ACID-BINDING PROTEIN ,Comorbidity ,030204 cardiovascular system & hematology ,VARIANTS ,Cardiovascular ,Bioinformatics ,Medical and Health Sciences ,0302 clinical medicine ,Risk Factors ,2.1 Biological and endogenous factors ,ARTERY-DISEASE ,Molecular Targeted Therapy ,Aetiology ,health care economics and organizations ,11 Medical and Health Sciences ,Genetics & Heredity ,RISK ,Metabolic Syndrome ,0303 health sciences ,CHD Exome+ Consortium ,Diabetes ,Single Nucleotide ,Biological Sciences ,3. Good health ,Europe ,Heart Disease ,MENDELIAN RANDOMIZATION ,Medical genetics ,Life Sciences & Biomedicine ,Type 2 ,Metabolic Networks and Pathways ,Asian Continental Ancestry Group ,medicine.medical_specialty ,endocrine system ,Asia ,education ,European Continental Ancestry Group ,Mutation, Missense ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,EPIC-CVD Consortium ,GENETIC ARCHITECTURE ,03 medical and health sciences ,Asian People ,Clinical Research ,Mendelian randomization ,Diabetes Mellitus ,Genetics ,Genetic predisposition ,medicine ,Humans ,Genetic Predisposition to Disease ,Obesity ,Genetic variability ,cardiovascular diseases ,Polymorphism ,GENOME-WIDE ASSOCIATION ,Heart Disease - Coronary Heart Disease ,Metabolic and endocrine ,METAANALYSIS ,AP2 ,030304 developmental biology ,Science & Technology ,Human Genome ,nutritional and metabolic diseases ,Odds ratio ,06 Biological Sciences ,medicine.disease ,HLA-DRB5 Chains ,Michigan Biobank ,030104 developmental biology ,ATHEROSCLEROSIS ,Diabetes Mellitus, Type 2 ,Genetic Loci ,Mutation ,Missense ,human activities ,Biomarkers ,Genome-Wide Association Study ,Developmental Biology - Abstract
Danish Saleheen, Benjamin Voight and colleagues perform genome-wide analysis of multi-ancestry cohorts to identify genetic associations with type 2 diabetes (T2D) and coronary heart disease (CHD). They find novel loci and show that 24% of T2D loci are also associated with CHD and that greater genetic risk of T2D increases risk of CHD. To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D–CHD analysis identified eight variants—two of which are coding—where T2D and CHD associations appear to colocalize, including a new joint T2D–CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.
- Published
- 2017
48. Common coding variant in SERPINA1 increases the risk for large artery stroke
- Author
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Malik, R, Dau, T, Gonik, M, Sivakumar, A, Deredge, DJ, Edeleva, EV, Götzfried, J, Van Der Laan, SW, Pasterkamp, G, Beaufort, N, Seixas, S, Bevan, S, Lincz, LF, Holliday, EG, Burgess, AI, Rannikmäe, K, Minnerup, J, Kriebel, J, Waldenberger, M, Müller-Nurasyid, M, Lichtner, P, Saleheen, D, Woo, D, Debette, S, Maguire, J, Cole, JW, Majersik, J, Jimenez-Conde, J, Lee, JM, Rost, N, Pare, G, Jern, C, Lindgren, AG, Cardenas, IF, Rothwell, PM, Levi, C, Attia, J, Sudlow, CLM, Braun, D, Markus, HS, Wintrode, PL, Berger, K, Jenne, DE, and Dichgans, M
- Subjects
Repressor Proteins ,Stroke ,alpha 1-Antitrypsin ,Humans ,Deuterium Exchange Measurement ,Leukocyte Elastase ,3' Untranslated Regions ,Polymorphism, Single Nucleotide ,Histone Deacetylases ,Mass Spectrometry ,Genetic Association Studies ,Plaque, Atherosclerotic - Abstract
Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis.
- Published
- 2017
49. Evaluation of clinical and inflammatory profile in opioid addiction patients with comorbid pain: results from a multicenter investigation
- Author
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Dennis BB, Samaan MC, Bawor M, Paul J, Plater C, Pare G, Worster A, Varenbut M, Daiter J, Marsh DC, Desai D, Thabane L, and Samaan Z
- Subjects
mental disorders ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Neurology. Diseases of the nervous system ,RC346-429 ,RC321-571 - Abstract
Brittany B Dennis,1 M Constantine Samaan,2 Monica Bawor,3 James Paul,4 Carolyn Plater,5 Guillaume Pare,1 Andrew Worster,6 Michael Varenbut,5 Jeff Daiter,5 David C Marsh,5,7 Dipika Desai,8 Lehana Thabane,1,9,10 Zainab Samaan1,8,11 1Department of Clinical Epidemiology and Biostatistics, 2Department ofPediatrics, Division of Pediatric Endocrinology, 3McMaster Integrative Neuroscience Discovery and Study Program, 4Department of Anesthesia, McMaster University, Hamilton, 5Ontario Addiction Treatment Centres, Richmond Hill, 6Department of Medicine, Hamilton General Hospital, Hamilton, 7Northern Ontario School of Medicine, Sudbury, 8Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, 9Centre for Evaluation of Medicine, 10System Linked Research Unit, Hamilton, 11Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada Background: Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT), with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population.Methods: The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235) on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and chemokine (C–C motif) ligand 2 [CCL2]). The study objectives were addressed using a descriptive statistical summary and a multivariable logistic regression model constructed in STATA version 12.Results: Among the participants eligible for inclusion (n=235), serum IFN-γ level and substance abuse behavior proved to be important delineating characteristics for the detection of comorbid pain. Analysis of inflammatory profile showed IFN-γ to be significantly elevated among patients reporting comorbid pain (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.17, 3.50; P=0.01). Patients reporting comorbid pain were also found to have an increase in positive opioid urine screens (OR: 1.02; 95% CI: 1.00, 1.03; P=0.01), indicating an increase in illicit opioid consumption.Conclusion: MMT patients with comorbid pain were shown to have elevated IFN-γ and higher rates of continued opioid abuse. The ability to objectively distinguish between patients with comorbid pain may help to both improve the prediction of poor responders to MMT as well as identify treatment approaches such as anti-inflammatory medications as safe alternatives for MMT patients with comorbid pain. Keywords: methadone maintenance treatment, inflammatory markers, TNF-α, IFN-γ, interleukins, CCL2, Brief Pain Inventory, opioid dependence
- Published
- 2014
50. Genetic influence on methadone treatment outcomes in patients undergoing methadone maintenance treatment for opioid addiction: a pilot study
- Author
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Samaan Z, Bawor M, Dennis BB, Plater C, Varenbut M, Daiter J, Worster A, Marsh DC, Tan C, Desai D, Thabane L, and Pare G
- Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry ,Neurology. Diseases of the nervous system ,RC346-429 ,RC321-571 - Abstract
Zainab Samaan,1–4 Monica Bawor,3,4 Brittany B Dennis,2,3 Carolyn Plater,5 Michael Varenbut,5 Jeffrey Daiter,5 Andrew Worster,5,6 David C Marsh,5,7 Charlie Tan,8 Dipika Desai,3 Lehana Thabane,2,9,10 Guillaume Pare11 1Department of Psychiatry and Behavioural Neurosciences, 2Department of Clinical Epidemiology and Biostatistics, 3Population Genomics Program, Chanchlani Research Centre, 4MiNDS Neuroscience Program, McMaster University, Hamilton, Ontario, Canada; 5Ontario Addiction Treatment Centres, Richmond Hill, Ontario, Canada; 6Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 7Northern Ontario School of Medicine, Laurentian University, Sudbury, Ontario, Canada; 8Michael G. DeGroote School of Medicine, McMaster University, 9Biostatistics Unit, Centre for Evaluation of Medicine, 10System Linked Research Unit, 11Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada Introduction: Treatment of opioid addiction with methadone is effective; however, it is known to produce interindividual variability. This may be influenced in part by genetic variants, which can increase the initial risk of developing opioid addiction as well as explain differences in response to treatment. This pilot study aimed to assess the feasibility of conducting a full-scale genetic analysis to identify genes that predict methadone treatment outcomes in this population. Methods: This was a cross-sectional observational study of patients admitted to a methadone maintenance treatment program for opioid addiction. We obtained demographic and clinical characteristics in addition to blood and urine samples, for the assessment of treatment outcomes. Results: The recruitment process yielded 252 patients, representing a 20% recruitment rate. We conducted genetic testing based on a 99.6% rate of provision of DNA samples. The average retention in treatment was 3.4 years, and >50% of the participants reported psychiatric and medical comorbidities. BDNF rs6265 and DRD2 rs1799978 were the common single nucleotide polymorphisms (SNPs) selected for the feasibility study. Discussion: This study met our predetermined feasibility criteria; recruitment, response rates, and genetic testing were feasible; treatment duration was sufficient for follow up; and the prevalence of comorbid conditions indicated the need for reliable psychiatric and chronic pain measures. The study strengths included effective collaboration with clinics and the generalizability of sample population. Key learning points show the need for assessment of treatment outcomes on multiple domains, implementation of follow up, and the development of standardized training for the study clinical staff. Keywords: genetics, substitute opioid therapy, treatment response, risk factors
- Published
- 2014
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