التفاصيل البيبلوغرافية
| العنوان: |
Stroke genetics informs drug discovery and risk prediction across ancestries |
| المؤلفون: |
Mishra, A, Malik, R, Hachiya, T, Jürgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Jackson, RD, Nielsen, JB, Giulianini, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Parodi, L, Rosand, J, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O’Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Sabatine, MS, Bae, H-J, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, Van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, Sacco, RL, Van Oostenbrugge, RJ, Chauhan, G, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Mägi, R, Nelis, M, Irvin, MR, Saleheen, D, De Leeuw, F-E, Levi, CR, Chong, MR, Maguire, J, Jiménez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmäe, K, Schmidt, R, Slowik, A, Sandset, EC, Pera, J, Thijs, VNS, Lindgren, AG, Tomppo, L, Ilinca, A, Melander, O, Engström, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Salomaa, V, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Akinyemi, R, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Sargurupremraj, M, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Roshchupkin, GV, Cushman, M, Jood, K, McDonough, CW, Bell, S, Sasaki, M, Linkohr, B, Lee, T-H, Putaala, J, Anderson, CD, Lopez, OL, Jian, X, Habib, N, Schminke, U, Cullell, N, Delgado, P, Satizabal, CL, Ibañez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muiño, E, Roquer, J, Jee, YH, Sarnowski, C, Sattar, N, Schmidt, CO, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Thomassen, JQ, Almgren, P, Georgakis, MK, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, De Bakker, PIW, DeStefano, AL, Abedi, V, Shimizu, A, Den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Smith, NL, Cárcel-Márquez, J, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Lemmens, R, Leys, D, Lin, W-Y, Lorentzen, E, Sloane, KL, Magnusson, PK, Nygaard, M, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Sutoh, Y, Tzourio, C, Van Duijn, CM, Leonard, HL, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Sun, YV, Bustamante, M, Caso, V, Choi, SH, Yang, C, Chowhan, A, Dartigues, J-F, Delavaran, H, Dörr, M, Ford, I, Gurpreet, WS, Tanno, K, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Yonova-Doing, E, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Tiedt, S, Laurie, CC, Li, L, Lind, L, Lindgren, CM, Makoto, H, Knol, MJ, Minegishi, N, Morris, AP, Müller-Nurasyid, M, Norrving, B, Tatlisumak, T, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Lewis, AJ, Rabionet, R, Riba-Llena, I, Ribasés, M, Torres-Aguila, NP, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, Á, Judy, RL, Smith, A, Stine, OC, Tiwari, HK, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, Ago, T, Van der Lee, SJ, Caro, I, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Amouyel, P, Trégouët, D-A, Sobue, K, Soriano-Tárraga, C, Völzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Trompet, S, Armstrong, ND, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Tuladhar, AM, Olalere, A, Bakker, MK, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Tybjærg-Hansen, A, Chen, Y, Fairhurst-Hunter, Z, Bartz, TM, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Van Vugt, M, Ferreira, LE, Nagai, A, Murakami, Y, Bennett, DA, Geerlings, MI, Gasca, NC, Gudnason, V, Shiroma, EJ, Vibo, R, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Bis, JC, Fongang, B, Wang, R, Ikram, MK, Völker, U, De Jager, PL, Verma, SS, De Cid, R, Nordestgaard, BG, De Laat, KF, Bordes, C, Van Norden, AGW, De Kort, PL, Vermeer, SE, Brouwers, PJAM, Wiggins, KL, Gons, RAR, Den Heijer, T, Van Dijk, GW, Van Rooij, FGW, Aamodt, AH, Børte, S, Skogholt, AH, Brumpton, BM, Willer, CJ, Wennberg, P, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjær, H, Zhou, W, Cain, A, Martinsen, AE, Kristoffersen, ES, Woo, D, Hveem, K, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethüm, K, Gallego-Fabrega, C, Lledós, M, Ridker, PM, Llucià-Carol, L, Krebs, K, Sobrino, T, Campos, F, Castillo, J, Freijó, M, Arenillas, JF, Obach, V, Álvarez-Sabín, J, Molina, CA, Ribó, M, Cho, K, Wilson, PWF, Muñoz-Narbona, L, Lopez-Cancio, E, Millán, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Xu, H, Chen, Z, Prats-Sánchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Martí-Fàbregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Yang, Q, Kamstrup, PR, Cruchaga, C, Van Setten, J, Van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Yoon, K, Sung, YJ, Cole, JW, Saillour-Glenisson, F, Gravel, S, Onland-Moret, NC, Heath, AK, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Lee, J-M, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Cheng, Y-C, Kõrv, J, França, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, Endres, M, Liman, T, Haeusler, KG, Ruigrok, YM, Meschia, JF, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Paré, G, Damrauer, SM, Chasman, DI, Rotter, JI, Chen, WM, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernández-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Sale, MM, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Hata, J, He, J, Liaw, Y-C, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Zonderman, AB, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Evans, MK, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Wilson, JG, O’Donnell, MJ, Okada, Y, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Correa, A, Traylor, M, Lewis, CM, Carty, CL, Reiner, A, Haessler, J, Langefeld, CD, Vaura, FC, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Lin, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Van Hylckama Vlieg, A, De Andrade, M, Brody, JA, Pattee, JW, Winsvold, BS, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Srinivasasainagendra, V, Pankratz, N |
| المصدر: |
123 ; 115 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2022 |
| المجموعة: |
Imperial College London: Spiral |
| مصطلحات موضوعية: |
Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, GENOME-WIDE ASSOCIATION, MENDELIAN RANDOMIZATION, POLYGENIC RISK, HERITABILITY, STATISTICS, EXPRESSION, BRAIN, ATLAS, REGULARIZATION, METAANALYSIS, Humans, Brain Ischemia, Drug Discovery, Genetic Predisposition to Disease, Genome-Wide Association Study, Ischemic Stroke, Molecular Targeted Therapy, Multifactorial Inheritance, Europe, Far East, Africa, COMPASS Consortium, INVENT Consortium, Dutch Parelsnoer Initiative (PSI) Cerebrovascular Disease Study Group, Estonian Biobank, PRECISE4Q Consortium, FinnGen Consortium |
| الوصف: |
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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| تدمد: |
0028-0836 |
| العلاقة: |
Nature; http://hdl.handle.net/10044/1/100004Test |
| DOI: |
10.1038/s41586-022-05165-3 |
| الإتاحة: |
https://doi.org/10.1038/s41586-022-05165-3Test
http://hdl.handle.net/10044/1/100004Test |
| حقوق: |
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0Test/. ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.81958CD2 |
| قاعدة البيانات: |
BASE |
