1. Serum magnesium and calcium levels in relation to ischemic stroke Mendelian randomization study
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Susanna C. Larsson, Matthew Traylor, Stephen Burgess, Giorgio B. Boncoraglio, Christina Jern, Karl Michaëlsson, Hugh S. Markus, Rainer Malik, Ganesh Chauhan, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab HH Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, raci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Daniel I Chasman, Wei-Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul IW de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Jeffrey Haessler, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Susan R Heckbert, Elizabeth G Holliday, George Howard, Fang-Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei-Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O'Donnell, Bruce M Psaty, Sara L Pulit, Kristiina Rannikmäe, Alexander P Reiner, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Paul M Ridker, Natalia S Rost, Peter M Rothwell, Jerome I Rotter, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie LM Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent NS Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil-Smoller, James G Wilson, Kerri L Wiggins, Qiong Yang, Salim Yusuf, Najaf Amin, Hugo S Aparicio, Donna K Arnett, John Attia, Alexa S Beiser, Claudine Berr, Julie E Buring, Mariana Bustamante, Valeria Caso, Yu-Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean-François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J Koudstaal, Jerzy Krupinski, Daniel L Labovitz, Cathy C Laurie, Christopher R Levi, Linxin Li, Lars Lind, Cecilia M Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L Lopez, Hirata Makoto, Nicolas Martinez-Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P Morris, Elena Muiño, Martina Müller-Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A Parati, Leema Reddy Peddareddygari, Nancy L Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba-Llena, Marta Ribasés, Jose R Romero, Jaume Roquer, Anthony G Rudd, Antti-Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano-Tárraga, Tara Stanne, O Colin Stine, David J Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P Torres-Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G Uitterlinden, Einar M Valdimarsson, Sven J van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R Williams, Charles DA Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K Sanghera, Olle Melander, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna MM Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, Berr, Claudine, Unit of Cardiovascular and Nutritional Epidemiology [Stockholm, Sweden], Karolinska Institutet [Stockholm]-Institute of Environmental Medicine [Stockholm, Sweden], Stroke Research Group [London, UK] (Department of Brain Repair and Rehabilitation), University of London - UCL [London, UK], MRC Biostatistics Unit [Cambridge, UK], University of Cambridge [UK] (CAM), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, Department of Surgical Sciences [Uppsala, Sweden], This work was supported by the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council. Hugh Markus is supported by an NIHR Senior Investigator award. His and Matthew Traylor’s work is supported by infrastructural support from the Cambridge University Hospitals Trust NIHR Biomedical Research Centre., MEGASTROKE project of the International Stroke Genetics Consortium : Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HH, Ago T, Almgren P, Amouyel P, Ay H, Bartz RM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD Jr, Butterworth AS, Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A, Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PI, DeStefano AL, Hoed MD, 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 FC, Hyacinth HI, Ikram MA, Ingelsson E, Irvin MR, Jian X, Jiménez-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 JM, Lemmens R, Leys D, Lewis CM, Lin WY, 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, Rannikmäe 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 CL, Tanislav C, Tatlisumak T, Taylor KD, Thijs VN, 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, Amin N, Aparicio HS, Arnett DK, Attia J, Beiser AS, Berr C, Buring JE, Bustamante M, Caso V, Cheng YC, Choi SH, Chowhan A, Cullell N, Dartigues JF, Delavaran H, Delgado P, Dörr M, Engström G, Ford I, Gurpreet WS, Hamsten A, Heitsch L, Hozawa A, Ibanez L, Ilinca A, Ingelsson M, Iwasaki M, Jackson RD, Jood K, Jousilahti P, Kaffashian S, Kalra L, Kamouchi M, Kitazono T, Kjartansson O, Kloss M, Koudstaal PJ, Krupinski J, Labovitz DL, Laurie CC, Levi CR, Li L, Lind L, Lindgren CM, Lioutas V, Liu YM, Lopez OL, Makoto H, Martinez-Majander N, Matsuda K, Minegishi N, Montaner J, Morris AP, Muiño E, Müller-Nurasyid M, Norrving B, Ogishima S, Parati EA, Peddareddygari LR, Pedersen NL, Pera J, Perola M, Pezzini A, Pileggi S, Rabionet R, Riba-Llena I, Ribasés M, Romero JR, Roquer J, Rudd AG, Sarin AP, Sarju R, Sarnowski C, Sasaki M, Satizabal CL, Satoh M, Sattar N, Sawada N, Sibolt G, Sigurdsson Á, Smith A, Sobue K, Soriano-Tárraga C, Stanne T, Stine OC, Stott DJ, Strauch K, Takai T, Tanaka H, Tanno K, Teumer A, Tomppo L, Torres-Aguila NP, Touze E, Tsugane S, Uitterlinden AG, Valdimarsson EM, van der Lee SJ, Völzke H, Wakai K, Weir D, Williams SR, Wolfe CD, Wong Q, Xu H, Yamaji T, Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth WT Jr, 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 JM, Kamatani Y, Debette S, Dichgans M., Larsson, Susanna C [0000-0003-0118-0341], Apollo - University of Cambridge Repository, and Neurology
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medicine.medical_specialty ,Neurology ,Heredity ,Neurologi ,[SDV]Life Sciences [q-bio] ,chemistry.chemical_element ,Calcium ,Polymorphism, Single Nucleotide ,Gastroenterology ,Article ,Brain Ischemia ,Brain ischemia ,03 medical and health sciences ,0302 clinical medicine ,Human genetics ,Internal medicine ,Mendelian randomization ,Medicine ,Humans ,Magnesium ,030212 general & internal medicine ,Stroke ,Herència (Biologia) ,Genètica humana ,business.industry ,Neurosciences ,Mendelian Randomization Analysis ,Odds ratio ,medicine.disease ,Confidence interval ,3. Good health ,[SDV] Life Sciences [q-bio] ,Intracranial Embolism ,chemistry ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Neurovetenskaper - Abstract
Comment inThe yin and yang of magnesium and calcium: New genetic insights for stroke? [Neurology. 2019]; International audience; Objective To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach. Methods Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases). Results In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10 −4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10 −4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype. Conclusions This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.
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- 2019