Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

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 H.H. Adams; Tetsuro Ago; Peter Almgren; Philippe Amouyel; Hakan Ay; Raci M. Bartz; Oscar R. Benavente; Steve Bevan; 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 I.W. 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 L.M. Sudlow; Christian Tanislav; Turgut Tatlisumak; Kent D. Taylor; Vincent N.S. 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 D.A. 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; Joanna M.M. Howson; Yoichiro Kamatani; Stephanie Debette; Martin Dichgans

doi:10.1212/WNL.0000000000007001

Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

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 H.H. Adams, Tetsuro AgoPeter Almgren, Philippe Amouyel, Hakan Ay, Raci M. Bartz, Oscar R. Benavente, Steve Bevan, 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 I.W. 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 L.M. Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D. Taylor, Vincent N.S. 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 D.A. 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, Joanna M.M. Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans

College of Public Health

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses 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).ResultsIn 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.ConclusionsThis 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.

Original language	English
Pages (from-to)	E944-E950
Journal	Neurology
Volume	92
Issue number	9
DOIs	https://doi.org/10.1212/WNL.0000000000007001
State	Published - Feb 26 2019

Bibliographical note

Publisher Copyright:
© 2019 American Academy of Neurology.

Funding

The Article Processing Charge was funded by the Swedish Research Council for Health, Working Life and Welfare (Forte). The authors thank the International Stroke Genetics Consortium for providing summary statistics data from the MEGASTROKE project. The MEGASTROKE authors are listed in the supplement. The MEGASTROKE project received funding from sources specified at megastroke.org/acknowledgments.html.

Funders	Funder number
National Institute for Health Research
Japan Society for the Promotion of Science	17H04143, 16K00385
Japan Society for the Promotion of Science
Vetenskapsrådet
Forskningsrådet om Hälsa, Arbetsliv och Välfärd
NIHR Cambridge Biomedical Research Centre

ASJC Scopus subject areas

Clinical Neurology

Access to Document

10.1212/WNL.0000000000007001

Cite this

Larsson, S. C., Traylor, M., Burgess, S., Boncoraglio, G. B., Jern, C., Michaëlsson, K., Markus, H. S., Malik, R., Chauhan, G., Sargurupremraj, M., Okada, Y., Mishra, A., Rutten-Jacobs, L., Giese, A. K., Van Der Laan, S. W., Gretarsdottir, S., Anderson, C. D., Chong, M., Adams, H. H. H., ... Dichgans, M. (2019). Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study. Neurology, 92(9), E944-E950. https://doi.org/10.1212/WNL.0000000000007001

@article{504086d7be3a4e8893873c5556a1ab82,

title = "Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study",

abstract = "ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses 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).ResultsIn 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.ConclusionsThis 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.",

author = "Larsson, {Susanna C.} and Matthew Traylor and Stephen Burgess and Boncoraglio, {Giorgio B.} and Christina Jern and Karl Micha{\"e}lsson and Markus, {Hugh S.} and Rainer Malik and Ganesh Chauhan and Muralidharan Sargurupremraj and Yukinori Okada and Aniket Mishra and Loes Rutten-Jacobs and Giese, {Anne Katrin} and {Van Der Laan}, {Sander W.} and Solveig Gretarsdottir and Anderson, {Christopher D.} and Michael Chong and Adams, {Hieab H.H.} and Tetsuro Ago and Peter Almgren and Philippe Amouyel and Hakan Ay and Bartz, {Raci M.} and Benavente, {Oscar R.} and Steve Bevan and Brown, {Robert D.} and Butterworth, {Adam S.} and Caty Carrera and Carty, {Cara L.} and Chasman, {Daniel I.} and Chen, {Wei Min} and Cole, {John W.} and Adolfo Correa and Ioana Cotlarciuc and Carlos Cruchaga and John Danesh and {De Bakker}, {Paul I.W.} and Destefano, {Anita L.} and Hoed, {Marcel Den} and Qing Duan and Engelter, {Stefan T.} and Falcone, {Guido J.} and Gottesman, {Rebecca F.} and Grewal, {Raji P.} and Vilmundur Gudnason and Stefan Gustafsson and Jeffrey Haessler and Harris, {Tamara B.} and Ahamad Hassan and Havulinna, {Aki S.} and Heckbert, {Susan R.} and Holliday, {Elizabeth G.} and George Howard and Hsu, {Fang Chi} and Hyacinth, {Hyacinth I.} and Ikram, {M. Arfan} and Erik Ingelsson and Irvin, {Marguerite R.} and Xueqiu Jian and Jordi Jim{\'e}nez-Conde and Johnson, {Julie A.} and Jukema, {J. Wouter} and Masahiro Kanai and Keene, {Keith L.} and Kissela, {Brett M.} and Kleindorfer, {Dawn O.} and Charles Kooperberg and Michiaki Kubo and Lange, {Leslie A.} and Langefeld, {Carl D.} and Claudia Langenberg and Launer, {Lenore J.} and Lee, {Jin Moo} and Robin Lemmens and Didier Leys and Lewis, {Cathryn M.} and Lin, {Wei Yu} and Lindgren, {Arne G.} and Erik Lorentzen and Magnusson, {Patrik K.} and Jane Maguire and Ani Manichaikul and McArdle, {Patrick F.} and Meschia, {James F.} and Mitchell, {Braxton D.} and Mosley, {Thomas H.} and Nalls, {Michael A.} and Toshiharu Ninomiya and O'Donnell, {Martin J.} and Psaty, {Bruce M.} and Pulit, {Sara L.} and Kristiina Rannikm{\"a}e and Reiner, {Alexander P.} and Rexrode, {Kathryn M.} and Kenneth Rice and Rich, {Stephen S.} and Ridker, {Paul M.} and Rost, {Natalia S.} and Rothwell, {Peter M.} and Rotter, {Jerome I.} and Tatjana Rundek and Sacco, {Ralph L.} and Saori Sakaue and Sale, {Michele M.} and Veikko Salomaa and Sapkota, {Bishwa R.} and Reinhold Schmidt and Schmidt, {Carsten O.} and Ulf Schminke and Pankaj Sharma and Agnieszka Slowik and Sudlow, {Cathie L.M.} and Christian Tanislav and Turgut Tatlisumak and Taylor, {Kent D.} and Thijs, {Vincent N.S.} and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Steffen Tiedt and Stella Trompet and Christophe Tzourio and {Van Duijn}, {Cornelia M.} and Matthew Walters and Wareham, {Nicholas J.} and Sylvia Wassertheil-Smoller and Wilson, {James G.} and Wiggins, {Kerri L.} and Qiong Yang and Salim Yusuf and Najaf Amin and Aparicio, {Hugo S.} and Arnett, {Donna K.} and John Attia and Beiser, {Alexa S.} and Claudine Berr and Buring, {Julie E.} and Mariana Bustamante and Valeria Caso and Cheng, {Yu Ching} and Choi, {Seung Hoan} and Ayesha Chowhan and Natalia Cullell and Dartigues, {Jean Fran{\c c}ois} and Hossein Delavaran and Pilar Delgado and Marcus D{\"o}rr and Gunnar Engstr{\"o}m and Ian Ford and Gurpreet, {Wander S.} and Anders Hamsten and Laura Heitsch and Atsushi Hozawa and Laura Ibanez and Andreea Ilinca and Martin Ingelsson and Motoki Iwasaki and Jackson, {Rebecca D.} and Katarina Jood and Pekka Jousilahti and Sara Kaffashian and Lalit Kalra and Masahiro Kamouchi and Takanari Kitazono and Olafur Kjartansson and Manja Kloss and Koudstaal, {Peter J.} and Jerzy Krupinski and Labovitz, {Daniel L.} and Laurie, {Cathy C.} and Levi, {Christopher R.} and Linxin Li and Lars Lind and Lindgren, {Cecilia M.} and Vasileios Lioutas and Liu, {Yong Mei} and Lopez, {Oscar L.} and Hirata Makoto and Nicolas Martinez-Majander and Koichi Matsuda and Naoko Minegishi and Joan Montaner and Morris, {Andrew P.} and Elena Mui{\~n}o and Martina M{\"u}ller-Nurasyid and Bo Norrving and Soichi Ogishima and Parati, {Eugenio A.} and Peddareddygari, {Leema Reddy} and Pedersen, {Nancy L.} and Joanna Pera and Markus Perola and Alessandro Pezzini and Silvana Pileggi and Raquel Rabionet and Iolanda Riba-Llena and Marta Ribas{\'e}s and Romero, {Jose R.} and Jaume Roquer and Rudd, {Anthony G.} and Sarin, {Antti Pekka} and Ralhan Sarju and Chloe Sarnowski and Makoto Sasaki and Satizabal, {Claudia L.} and Mamoru Satoh and Naveed Sattar and Norie Sawada and Gerli Sibolt and {\'A}sgeir Sigurdsson and Albert Smith and Kenji Sobue and Carolina Soriano-T{\'a}rraga and Tara Stanne and Stine, {O. Colin} and Stott, {David J.} and Konstantin Strauch and Takako Takai and Hideo Tanaka and Kozo Tanno and Alexander Teumer and Liisa Tomppo and Torres-Aguila, {Nuria P.} and Emmanuel Touze and Shoichiro Tsugane and Uitterlinden, {Andre G.} and Valdimarsson, {Einar M.} and {Van Der Lee}, {Sven J.} and Henry V{\"o}lzke and Kenji Wakai and David Weir and Williams, {Stephen R.} and Wolfe, {Charles D.A.} and Quenna Wong and Huichun Xu and Taiki Yamaji and Sanghera, {Dharambir K.} and Olle Melander and Daniel Strbian and Israel Fernandez-Cadenas and Longstreth, {W. T.} and Arndt Rolfs and Jun Hata and Daniel Woo and Jonathan Rosand and Guillaume Pare and Hopewell, {Jemma C.} and Danish Saleheen and Kari Stefansson and Worrall, {Bradford B.} and Kittner, {Steven J.} and Sudha Seshadri and Myriam Fornage and Howson, {Joanna M.M.} and Yoichiro Kamatani and Stephanie Debette and Martin Dichgans",

note = "Publisher Copyright: {\textcopyright} 2019 American Academy of Neurology.",

year = "2019",

month = feb,

day = "26",

doi = "10.1212/WNL.0000000000007001",

language = "English",

volume = "92",

pages = "E944--E950",

number = "9",

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Larsson, SC, Traylor, M, Burgess, S, Boncoraglio, GB, Jern, C, Michaëlsson, K, Markus, HS, Malik, R, Chauhan, G, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, Van Der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, RM, Benavente, OR, Bevan, S, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, 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, 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, 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, CDA, Wong, Q, Xu, H, Yamaji, T, Sanghera, DK, Melander, O, 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, Howson, JMM, Kamatani, Y, Debette, S & Dichgans, M 2019, 'Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study', Neurology, vol. 92, no. 9, pp. E944-E950. https://doi.org/10.1212/WNL.0000000000007001

TY - JOUR

T1 - Serum magnesium and calcium levels in relation to ischemic stroke

T2 - Mendelian randomization study

AU - Larsson, Susanna C.

AU - Traylor, Matthew

AU - Burgess, Stephen

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AU - Dichgans, Martin

PY - 2019/2/26

Y1 - 2019/2/26

N2 - ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses 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).ResultsIn 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.ConclusionsThis 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.

AB - ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses 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).ResultsIn 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.ConclusionsThis 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.

UR - http://www.scopus.com/inward/record.url?scp=85062192232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062192232&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000007001

DO - 10.1212/WNL.0000000000007001

M3 - Article

C2 - 30804065

AN - SCOPUS:85062192232

SN - 0028-3878

VL - 92

SP - E944-E950

JO - Neurology

JF - Neurology

IS - 9

ER -

Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

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