المؤلفون: Valdes-Marquez, E., Parish, S. (Sharon), Clarke, R., Stari, T., Worrall, B.B. (Bradford B.), Hopewell, J.

المصدر: Neurology vol. 92 no. 11, pp. E1176-E1187

الوصف: 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 ×

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/116340Test; urn:hdl:1765/116340

الإتاحة: https://doi.org/10.1212/wnl.0000000000007091Test
http://repub.eur.nl/pub/116340Test

المؤلفون: 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)

المصدر: Nature Communications vol. 9 no. 1

الوصف: 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.

وصف الملف: application/pdf

العلاقة: info:eu-repo/grantAgreement/EC/FP7/601456; http://repub.eur.nl/pub/112872Test; urn:hdl:1765/112872

الإتاحة: https://doi.org/10.1038/s41467-018-07340-5Test
http://repub.eur.nl/pub/112872Test

المؤلفون: Traylor, M. (Matthew), Malik, R. (Rainer), Nalls, M.A. (Michael), Cotlarciuc, I. (Ioana), Radmanesh, F. (Farid), Thorleifsson, G. (Gudmar), Hanscombe, K.B. (Ken B.), Langefeld, C.D. (Carl), Saleheen, D. (Danish), Rost, N.S. (Natalia), Yet, I. (Idil), Spector, T.D. (Timothy), Bell, J.T. (Jordana), Hannon, E. (Eilis), Mill, J. (Jonathan), Chauhan, G. (Ganesh), Debette, S. (Stéphanie), Bis, J.C. (Joshua), Longstreth Jr, W.T., Ikram, M.K. (Kamran), Launer, L.J. (Lenore), Seshadri, S. (Sudha), Hamilton-Bruce, M.A. (Monica Anne), Jimenez-Conde, J. (Jordi), Cole, J.W. (John W.), Schmidt, R. (Reinhold), Slowik, A. (Agnieszka), Lemmens, R. (Robin), Lindgren, A.G. (Arne G.), Melander, O. (Olle), Grewal, R.P. (Raji P.), Sacco, R.L. (Ralph), Rundek, T. (Tatjana), Rexrode, K. (Kathryn), Arnett, D.K. (Donna), Johnson, J.A. (Julie A.), Benavente, O.R. (Oscar R.), Wasssertheil-Smoller, S. (Sylvia), Lee, J.-M. (Jin-Moo), Pulit, S.L. (Sara), Wong, Q. (Quenna), Rich, S.S. (Stephen), Bakker, P.I.W. (Paul) de, McArdle, P.F. (Patrick), Woo, D. (Daniel), Anderson, C.D. (Christopher D.), Xu, H. (Huichun), Heitsch, L. (Laura), Fornage, M. (Myriam), Jern, C. (Christina), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Gretarsdottir, S. (Solveig), Lewis, C.M. (Cathryn), Sharma, P. (Pankaj), Sudlow, C. (Cathie), Rothwell, P.M. (Peter), Boncoraglio, G. (Giorgio Battista), Thijs, V. (Vincent), Levi, C. (Christopher), Meschia, J.F. (James F.), Rosand, J. (Jonathan), Kittner, T. (Thomas), Mitchell, B.D. (Braxton), Kubisch, C. (Christian), Worrall, B.B. (Bradford B.), Markus, H.S. (Hugh)

المصدر: Annals of Neurology vol. 81 no. 3, pp. 383-394

الوصف: Objective: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke. Methods: We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on messenger RNA (mRNA) expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. Results: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (odds ratio [OR; 95% confidence interval {CI}] = 1.16 [1.10–1.22]; p = 3.2 × 10−9). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05–1.16]; p = 5.3 × 10−5; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84–1.12]; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10−7) and DNA methylation at probe cg16596957

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/98794Test; urn:hdl:1765/98794

الإتاحة: https://doi.org/10.1002/ana.24840Test
http://repub.eur.nl/pub/98794Test

المؤلفون: Haycock, P. (Philip), Burgess, S. (Stephen), Nounu, A. (Aayah), Zheng, J. (Jie), Okoli, G.N. (George N.), Bowden, J., Wade, K.H. (Kaitlin Hazel), Timpson, N.J. (Nicholas J.), Evans, D.M. (David M.), Willeit, P. (Peter), Aviv, A. (Abraham), Gaunt, T.R. (Tom), Hemani, G., Mangino, M. (Massimo), Ellis, H.P. (Hayley Patricia), Kurian, K.M. (Kathreena M.), Pooley, K.A. (Karen A.), Eeles, R. (Rosalind), Lee, J.E. (Jeffrey E.), Fang, S. (Shenying), Chen, W.V. (Wei V.), Law, M.H. (Matthew H.), Bowdler, L.M. (Lisa M.), Iles, M.M. (Mark M.), Yang, Q. (Qiong Fang), Worrall, B.B. (Bradford B.), Markus, H.S. (Hugh), Hung, R.J. (Rayjean J.), Amos, W., Spurdle, A.B. (Amanda), Thompson, D. (Deborah), O'Mara, T.A. (Tracy A.), Wolpin, B. (Brian), Amundadottir, L. (Laufey), Stolzenberg-Solomon, R. (Rachael), Trichopoulou, A. (Antonia), Onland-Moret, N.C. (Charlotte), Lund, E. (Eiliv), Duell, E.J. (Eric), Canzian, F. (Federico), Severi, G. (Gianluca), Overvad, K. (Kim), Gunter, M.J. (Marc J.), Tumino, R. (Rosario), Svenson, U. (Ulrika), Rij, A.M. (Andre) van, Baas, A.F. (Annette), Bown, N., Samani, N.J. (Nilesh), Van t'Hof, F.N.G. (Femke N.G.), Tromp, G. (Gerard), Jones, G.T. (Gregory T.), Kuivaniemi, H. (Helena), Elmore, J.R. (James R.), Johansson, M. (Mattias), Mckay, J. (James), Scelo, G. (Ghislaine), Carreras-Torres, R. (Robert), Gaborieau, V. (Valerie), Brennan, P. (Paul), Bracci, P.M. (Paige M.), Neale, R.E. (Rachel E.), Olson, S.H. (Sara H.), Gallinger, S. (Steve), Li, D. (Donghui), Olson, S.H. (Sara), Risch, H. (Harvey), Klein, A.P. (Alison P.), Han, J., Abnet, C.C. (Christian C.), Freedman, N.D. (Neal D.), Taylor, P.R. (Phil R.), Maris, J.M. (John), Aben, K.K.H. (Katja), Kiemeney, L.A.L.M. (Bart), Vermeulen, S.H.H.M. (Sita), Wiencke, J.K. (John K.), Walsh, K.M. (Kyle M.), Wrensch, M. (Margaret), Rice, T. (Terri), Turnbull, C. (Clare), Litchfield, K. (Kevin), Paternoster, L. (Lavinia), Standl, M. (Marie), Abecasis, G.R. (Gonçalo), SanGiovanni, J.P. (John Paul), Li, Y. (Yong), Mijatovic, V. (Vladan), Sapkota, Y. (Yadav), Low, S.-K. (Siew-Kee), Zondervan, K.T. (Krina), Montgomery, G.W. (Grant W.), Nyholt, D.R. (Dale), Heel, D.A. (David) van, Hunt, K. (Karen), Arking, D.E. (Dan), Ashar, F.N. (Foram N.), Sotoodehnia, N. (Nona), Woo, D. (Daniel), Rosand, J. (Jonathan), Comeau, M.E. (Mary E.), Brown, W.M. (W. Mark), Silverman, E. (Edwin), Hokanson, J.E. (John E.), Cho, M.H. (Michael), Hui, J. (Jennie), Ferreira, M.A. (Manuel A.), Thompson, P.J. (Philip J.), Morrison, A.C. (Alanna), Felix, J.F. (Janine F.), Smith, N.L. (Nicholas L.), Christiano, A.M. (Angela), Petukhova, L. (Lynn), Betz, R.C. (Regina), Fan, X. (Xing), Zhang, X. (Xuejun), Zhu, C. (Caihong), Langefeld, C.D. (Carl), Thompson, S.D. (Susan D.), Wang, F. (Feijie), Lin, X. (Xu), Schwartz, D.A. (David A.), Fingerlin, T.E. (Tasha E.), Rotter, J.I. (Jerome I.), Cotch, M.F. (Mary Frances), Jensen, R.A. (Richard A.), Munz, M. (Matthias), Dommisch, H. (Henrik), Schaefer, A. (Antje), Han, F. (Fang), Ollila, H.M., Hillary, R.P. (Ryan P.), Albagha, O.M.E. (Omar M.), Ralston, S.H. (Stuart), Zeng, C. (Chenjie), Zheng, W. (Wei), Shu, X.-O. (Xiao-Ou), Reis, A. (André), Uebe, S. (Steffen), Hüffmeier, U. (Ulrike), Kawamura, Y. (Yoshiya), Otowa, T. (Takeshi), Sasaki, T. (Tsukasa), Hibberd, M.L. (Martin), Davila, S. (Sonia), Xie, G. (Gang), Siminovitch, K.A. (Katherine), Bei, J.-X. (Jin-Xin), Zeng, Y.X., Försti, A. (Asta), Chen, B. (Bowang), Landi, S. (Stefano), Franke, A. (Andre), Fischer, A. (Annegret), Ellinghaus, D. (David), Flores, C. (Carlos), Noth, I. (Imre), Ma, S.-F. (Shwu-Fan), Foo, J.-N. (Jia-Nee), Liu, J. (Jianjun), Kim, J.-W. (Jong-Won), Cox, D.G. (David), Delattre, O. (Olivier), Mirabeau, O. (Olivier), Skibola, C.F. (Christine F.), Tang, C.S. (Clara S.), Garcia-Barcelo, M., Chang, K.-P. (Kai-Ping), Su, W.-H. (Wen-Hui), Chang, Y.-S. (Yu-Sun), Martin, N.G. (Nicholas G.), Gordon, S.D. (Scott D.), Wade, T.D. (Tracey D.), Lee, C. (Chaeyoung), Kubo, M. (Michiaki), Cha, P.-C. (Pei-Chieng), Nakamura, Y. (Yusuke), Levy, D. (Daniel), Kimura, M. (Masayuki), Hwang, S.-J. (Shih-Jen), Hunt, S.C. (Steven), Spector, T.D. (Timothy), Soranzo, N. (Nicole), Manichaikul, A.W. (Ani W.), Barr, R.G. (Graham), Kahali, B. (Bratati), Speliotes, E.K. (Elizabeth), Yerges-Armstrong, L.M. (Laura), Cheng, C-Y. (Ching-Yu), Jonas, J.B. (Jost B.), Wong, T.Y. (Tien Yin), Fogh, I. (Isabella), Lin, K. (Kuang), Powell, J. (John), Rice, K. (Kenneth), Relton, C.L. (Caroline), Martin, R.M. (Richard M.), Smith, A.V. (Davey)

المصدر: JAMA oncology vol. 3 no. 5, pp. 636-651

الوصف: IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of ...

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/108628Test; urn:hdl:1765/108628

الإتاحة: https://doi.org/10.1001/jamaoncol.2016.5945Test
http://repub.eur.nl/pub/108628Test

المؤلفون: Cheng, Y.-C. (Yu-Ching), Stanne, T.M. (Tara M.), Giese, A.-K. (Anne-Katrin), Ho, W.K. (Weang K.), Traylor, M. (Matthew), Amouyel, P. (Philippe), Holliday, E.G. (Elizabeth), Malik, R. (Rainer), Xu, H. (Huichun), Kittner, T. (Thomas), Cole, J.W. (John W.), O´Connell, J.R., Danesh, J. (John), Rasheed, A. (Asif), Zhao, W. (Wei), Engelter, S.T. (Stefan), Grond-Ginsbach, C. (Caspar), Kamatani, Y. (Yoichiro), Lathrop, M. (Mark), Leys, D. (Didier), Thijs, V. (Vincent), Metso, T.M. (Tiina M.), Tatlisumak, T. (Turgut), Pezzini, A. (Alessandro), Parati, E.A. (Eugenio A.), Norrving, B. (Bo), Bevan, S. (Steve), Rothwell, P.M. (Peter), Sudlow, C. (Cathie), Slowik, A. (Agnieszka), Lindgren, A.G. (Arne G.), Walters, M. (Matthew), Jannes, J. (Jim), Shen, J. (Jess), Crosslin, D.R. (David), Doheny, K.F. (Kimberly), Laurie, C.C. (Cathy), Kanse, S.M. (Sandip ), Bis, J.C. (Joshua), Fornage, M. (Myriam), Mosley, T.H. (Thomas H.), Hopewell, J., Strauch, K. (Konstantin), Müller-Nurasyid, M. (Martina), Gieger, C. (Christian), Waldenberger, M. (Melanie), Peters, A. (Annette), Meisinger, C. (Christine), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Meschia, J.F. (James F.), Seshadri, S. (Sudha), Sharma, P. (Pankaj), Worrall, B.B. (Bradford B.), Jern, C. (Christina), Levi, C. (Christopher), Kubisch, C. (Christian), Boncoraglio, G. (Giorgio Battista), Markus, H.S. (Hugh), Debette, S. (Stéphanie), Rolfs, A. (Arndt), Saleheen, D., Mitchell, B.D. (Braxton)

المصدر: Stroke vol. 47 no. 2, pp. 307-316

مصطلحات موضوعية: Factor VII, Genetics, Genome-wide analysis, Ischemic stroke, Stroke

الوصف: Background and Purpose - Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early-versus late-onset str

العلاقة: info:eu-repo/grantAgreement/EC/FP7/201413; info:eu-repo/grantAgreement/EC/FP7/261123; http://repub.eur.nl/pub/90124Test; urn:hdl:1765/90124

الإتاحة: https://doi.org/10.1161/STROKEAHA.115.011328Test
http://repub.eur.nl/pub/90124Test

المؤلفون: Van Der Laan, S.W. (Sander W.), Fall, M. (Magnus), Soumaré, A. (Aicha), Teumer, A. (Alexander), Sedaghat, S. (Sanaz), Baumert, J. (Jens), Zabaneh, D. (Delilah), Setten, J. (Jessica) van, Isgum, I. (Ivana), Galesloot, T.E. (Tessel), Arpegård, J. (Johannes), Amouyel, P. (Philippe), Trompet, S. (Stella), Waldenberger, M. (Melanie), Dörr, M. (Marcus), Magnusson, P.K. (Patrik), Giedraitis, V. (Vilmantas), Larsson, A. (Anders), Morris, A.P. (Andrew), Felix, J.F. (Janine), Morrison, A.C. (Alanna C.), Franceschini, N. (Nora), Bis, J.C. (Joshua), Kavousi, M. (Maryam), O'Donnell, C.J. (Christopher), Drenos, F. (Fotios), Tragante, V. (Vinicius), Munroe, P. (Patricia), Malik, R. (Rainer), Kubisch, C. (Christian), Worrall, B.B. (Bradford B.), Erdmann, J. (Jeanette), Nelson, C.P. (Christopher P.), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Marchini, J. (Jonathan), Patel, R.S. (Riyaz), Hingorani, A. (Aroon), Kao, W.H.L. (Wen), Pedersen, N.L. (Nancy), Graaf, J. (Jacqueline) de, Kiemeney, L.A.L.M. (Bart), Baumeister, S.E. (Sebastian), Franco, O.H. (Oscar), Hofman, A. (Albert), Uitterlinden, A.G. (André), Koenig, W. (Wolfgang), Meisinger, C. (Christa), Peters, A. (Annette), Thorand, B. (Barbara), Jukema, J.W. (Jan Wouter), Eriksen, B.O. (Bjørn Odvar), Toft, I. (Ingrid), Wilsgaard, T. (Tom), Onland-Moret, N.C. (N. Charlotte), Schouw, Y.T. (Yvonne) van der, Debette, S. (Stéphanie), Kumari, M. (Meena), Svensson, P. (Per), van der Harst, P. (Pim), Kivimaki, M. (Mika), Keating, J. (John), Sattar, N. (Naveed), Dehghan, A. (Abbas), Reiner, A. (Alexander), Ingelsson, E. (Erik), Ruijter, H.M. (Hester ) den, Bakker, P.I.W. (Paul) de, Pasterkamp, G. (Gerard), Ärnlöv, J. (Johan), Holmes, M.V. (Michael), Asselbergs, F.W. (Folkert)

المصدر: Journal of the American College of Cardiology vol. 68 no. 9, pp. 934-945

مصطلحات موضوعية: coronary heart disease, genetics, heart failure, ischemic stroke

الوصف: __Background__ Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. __Objectives__ The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. __Methods__ We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. __Results__ Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10−14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10−211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10−5). A causal effect of cystatin C was not detected for any individual component of CVD. __Conclusions__ Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.

وصف الملف: application/pdf

العلاقة: info:eu-repo/grantAgreement/EC/FP7/601456; http://repub.eur.nl/pub/96928Test; urn:hdl:1765/96928

الإتاحة: https://doi.org/10.1016/j.jacc.2016.05.092Test
http://repub.eur.nl/pub/96928Test

المؤلفون: Achterberg, S. (Sefanja), Kappelle, L.J. (Jaap), Bakker, P.I.W. (Paul) de, Traylor, M. (Matthew), Algra, A. (Ale), Graaf, Y. (Yolanda) van der, Grobbee, D.E. (Diederick), Rutten, G.E.H.M. (Guy), Visseren, F.L.J. (Frank), Moll, F.L. (Frans), Mali, W.P. (Willem), Doevendans, P.A. (Pieter), Martin, F. (Farrall), Holliday, E.G. (Elizabeth), Sudlow, C. (Cathie), Hopewell, J., Cheng, Y.-C. (Yu-Ching), Fornage, M. (Myriam), Ikram, M.K. (Kamran), Malik, R. (Rainer), Bevan, S. (Steve), Thorsteinsdottir, U. (Unnur), DeStefano, A.L. (Anita), Worrall, B.B. (Bradford B.), Reiner, A. (Alexander), Mitchell, B.D. (Braxton), Clarke, R. (Robert), Levi, C. (Christopher), Seshadri, S. (Sudha), Boncoraglio, G. (Giorgio Battista), Sharma, P. (Pankaj), Bis, J.C. (Joshua), Gretarsdottir, S. (Solveig), Psaty, B.M. (Bruce), Rothwell, P.M. (Peter), Rosand, J. (Jonathan), Meschia, J.F. (James F.), Stefansson, K. (Kari), Kubisch, C. (Christian), Markus, H.S. (Hugh)

المصدر: PLoS ONE vol. 10 no. 4

الوصف: Background: Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results: We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke. Conclusions: We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events.

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/78910Test; urn:hdl:1765/78910

الإتاحة: https://doi.org/10.1371/journal.pone.0119203Test
http://repub.eur.nl/pub/78910Test

المؤلفون: Holliday, E.G. (Elizabeth), Traylor, M. (Matthew), Malik, R. (Rainer), Bevan, S. (Steve), Falcone, G.J. (Guido J.), Hopewell, J., Cheng, Y.-C. (Yu-Ching), Cotlarciuc, I. (Ioana), Bis, J.C. (Joshua), Boerwinkle, E.A. (Eric), Boncoraglio, G. (Giorgio Battista), Clarke, R. (Robert), Cole, J.W. (John W.), Fornage, M. (Myriam), Furie, K.L. (Karen), Ikram, M.A. (Arfan), Jannes, J. (Jim), Kittner, T. (Thomas), Lincz, L.F. (Lisa), Maguire, J.M. (Jane), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Nalls, M.A. (Michael), Oldmeadow, C. (Christopher), Parati, E.A. (Eugenio A.), Psaty, B.M. (Bruce), Rothwell, P.M. (Peter), Seshadri, S. (Sudha), Scott, R.J. (Rodney J.), Sharma, P. (Pankaj), Sudlow, C. (Cathie), Wiggins, K.L. (Kerri), Worrall, B.B. (Bradford B.), Rosand, J. (Jonathan), Mitchell, B.D. (Braxton), Kubisch, C. (Christian), Markus, H.S. (Hugh), Levi, C. (Christopher), Attia, J. (John), Wray, N.R. (Naomi)

المصدر: Stroke vol. 46 no. 3, pp. 615-619

مصطلحات موضوعية: Atherosclerosis, Genetic epidemiology, Lacunar stroke

الوصف: Background and Purpose: Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Methods: Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. Results: High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10-4) and profile scores (rg=0.72; 95% confide

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/86722Test; urn:hdl:1765/86722

الإتاحة: https://doi.org/10.1161/STROKEAHA.114.007930Test
http://repub.eur.nl/pub/86722Test

المؤلفون: Cotlarciuc, I. (Ioana), Malik, R. (Rainer), Holliday, E.G. (Elizabeth), Ahmadi, K.R. (Kourosh), Paré, G. (Guillaume), Psaty, B.M. (Bruce), Fornage, M. (Myriam), Hasan, N. (Nazeeha), Rinne, P.E. (Paul), Ikram, M.A. (Arfan), Markus, H.S. (Hugh), Rosand, J. (Jonathan), Mitchell, B.D. (Braxton), Kittner, T. (Thomas), Meschia, J.F. (James F.), Meurs, J.B.J. (Joyce) van, Uitterlinden, A.G. (André), Worrall, B.B. (Bradford B.), Kubisch, C. (Christian), Sharma, P. (Pankaj)

المصدر: Stroke vol. 45 no. 7, pp. 1920-1924

مصطلحات موضوعية: genetic association studies, genetic risk score, homocysteine, stroke

الوصف: BACKGROUND AND PURPOSE - : Elevated total plasma homocysteine (tHcy) levels are known to be associated with increased risk of ischemic stroke (IS). Given that both tHcy and IS are heritable traits, we investigated a potential genetic relationship between homocysteine levels and stroke risk by assessing 18 polymorphisms previously associated with tHcy levels for their association with IS and its subtypes. METHODS - : Previous meta-analysis results from an international stroke collaborative network, METASTROKE, were used to assess association of the 18 tHcy-associated single-nucleotide polymorphisms (SNPs) in 12 389 IS cases and 62 004 controls. We also investigated the associations in regions located within 50 kb from the 18 tHcy-related SNPs and the association of a genetic risk score, including the 18 SNPs. RESULTS - : One SNP located in the RASIP1 gene and a cluster of 3 SNPs located at and near SLC17A3 were significantly associated with IS (P<0.0003) after correcting for multiple testing. For stroke subtypes, the sentinel SNP located upstream of MUT was significantly associated with small-vessel disease (P=0.0022), whereas 1 SNP located in MTHFR was significantly associated with large-vessel dis

العلاقة: http://repub.eur.nl/pub/60572Test; urn:hdl:1765/60572

الإتاحة: https://doi.org/10.1161/STROKEAHA.114.005208Test
http://repub.eur.nl/pub/60572Test

المؤلفون: Dodd, C.N. (Caitlin), Romio, S.A. (Silvana), Black, S. (Steve), Vellozzi, C. (Claudia), Andrews, N.J. (Nick), Sturkenboom, M.C.J.M. (Miriam), Zuber, P. (Patrick), Hua, W. (Wei), Bonhoeffer, J. (Jan), Buttery, J. (Jim), Crawford, N. (Nigel), Deceuninck, G. (Genevieve), Vries, C.S. (Corinne) de, Wals, P. (Philippe) de, Gimeno, D. (David), Heijbel, H. (Harald), Hughes, H. (Hayley), Hur, K. (Kwan), Hviid, A. (Anders), Kelman, J. (Jeffrey), Kilpi, T. (Tehri), Chuang, S.K. (S.), Macartney, T. (Thomas), Rett, M. (Melisa), Lopez-Callada, V.R. (Vesta Richardson), Salmon, D. (Daniel), Sanchez, F.G. (Francisco Gimenez), Sanz, N. (Nuria), Silverman, B. (Bernard), Storsaeter, J. (Jann), Thirugnanam, U. (Umapathi), Maas, N.A.T. (Nicoline) van der, Yih, K. (Katherine), Zhang, T. (Teng Fei), Izurieta, H.S. (Hector), Addis, B.J., Akhtar, A. (Aysha), Cope, J. (Judith), Davis, R.L. (Robert), Gargiullo, P. (Paul), Kurz, X. (Xavier), Law, B. (Barbara), Sahinovic, I. (Isabelle), Tokars, J. (Jerry), Serrano, P. (Pedro), Cheng, A. (Aixin), Charles, P. (Pat), Clothier, H. (Hazel), Day, B. (Bruce), Day, T. (Timothy), Gates, P. (Peter), MacDonnell, R. (Richard), Roberts, L. (Les), Rodriguez-Casero, V. (Vic-toria), Wijeratne, T. (Tissa), Kiers, H.A.L. (Henk), Blyth, C. (Christopher), Booy, R. (Robert), Elliott, E. (Elizabeth), Gold, M.R. (Michael), Marshall, H., McIntyre, P. (Peter), Richmond, P. (Peter), Royle, J. (Jenny), Wood, N.W. (Nicholas), Zurynski, Y. (Yvonne), Calvo, G. (Gonzalo), Campins, M. (Magda), Corominas, N. (Nuria), Torres, F. (Ferran), Valls, V., Vilella, A. (Ángels), Dutra, A. (Amalia), Eick-Cost, A. (Angelia), Jackson, H.M. (Henry), Garman, K. (Katherine), Hu, Z. (Zheng), Rigo, J., Badoo, J. (Judith), Cho, D (David), Polakowski, L.L. (Laura), Sandhu, S.K. (Sukhminder), Sun, G. (Guoying), Chan, H.-S.S. (Hoi-Shan Sophelia), Chan, K.-Y. (Kwok-Yin), Cheung, R. (Raymond), Cheung, Y-F. (Yuk-Fai), Cherk, S. (Sharon), Chuang, S.K (S.), Fok, D. (Dennis), Fung, B.-H. (Bun-Hey), Ko, K.-F. (Kwai-Fu), Lau, K.W. (Ka Wing), Lau, K.-K. (Kwok-Kwong), Li, P. (Pulin), Liu, H.-T. (Hui-Tung), Liu, S.-H. (Shao-Haei), Mok, K. (Kin), So, J. (Joanna), Wong, W. (Winnie), Wu, S.-P. (Shun-Ping), Ball, R. (Robert), Burwen, D. (Dale), Franks, R.L. (Riley), Gibbs, J.M. (Jonathan), Kliman, R.E. (Rebecca), Kropp, S. (Silke), MaCurdy, T.E. (Thomas), Martin, D.B. (David), Sandhu, S.-D.K. (Sukhmin-Der), Worrall, B.B. (Bradford B.), Fuentes, D.E.F. (Dra. Elvira Fuentes), González, P.C.O. (Paola Carolina Ojeda), Reyna, V.F. (Valerie ), Kulldorff, M. (Martin), Lee, G. (Grace), Lieu, T.A. (Tracy), Platt, S., Serres, G.D. (Gaston De), Jabin, K. (Kamilah), Soh, B.L.S. (Bee Leng Sally), Arnheim-Dahlström, L. (Lisen), Castot, A. (Anne), Melker, H.E. (Hester) de, Dieleman, J.P. (Jeanne), Hallgren, J. (Jonal), Jacobs, B.C. (Bart), Johansen, K. (Kari), Kramarz, P (Piotr), Lapeyre, M. (Maryse), Leino, T. (Tuija), Mølgaard-Nielsen, D. (Ditte), Mosseveld, M. (Mees), Olberg, H.K. (Henning K), Sammon, C.-M. (Cor-Mac), Saussier, C. (Christel), Schuemie, M.J. (Martijn), Sommet, A. (Agnès), Sparen, P. (Pär), Svanström, H. (Henrik), Vanrolleghem, A.M. (Ann M.), Weibel, D.M. (Daniel), Domingo, J.D. (Javier Diez), Esparza, J.L. (José LuísMicó), Lucas, R.M.O. (Rafael M. Ortí), Maseres, J.B.M. (Juan B. Mollar), Sánchez, J.L.A. (José Luís Alfonso), Sánchez, M.G. (Mercedes Garcés), Viguer, V.Z. (Vicente Zanón), Cunningham, F. (Francesca), Avagyan, A. (Armen), Thakkar, B. (Bharat), Zhang, R. (Rongping)

المصدر: Vaccine vol. 31 no. 40, pp. 4448-4458

مصطلحات موضوعية: Adjuvant, Adverse events following immunization (AEFI), Guillain Barré Syndrome (GBS), International, Monovalent H1N1 Vaccine (H1N1), Self-controlled case-series method (SCCS)

الوصف: Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. Methods: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. Results: We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/73133Test; urn:hdl:1765/73133

الإتاحة: https://doi.org/10.1016/j.vaccine.2013.06.032Test
http://repub.eur.nl/pub/73133Test