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 & 237 others 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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish
Pages (from-to)E944-E950
JournalNeurology
Volume92
Issue number9
DOIs
Publication statusPublished - Feb 26 2019

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Random Allocation
Magnesium
Stroke
Calcium
Serum
Confidence Intervals
Odds Ratio
Mendelian Randomization Analysis
Single Nucleotide Polymorphism
Arteries

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Larsson, S. C., Traylor, M., Burgess, S., Boncoraglio, G. B., Jern, C., Michaëlsson, K., ... 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

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

In: Neurology, Vol. 92, No. 9, 26.02.2019, p. E944-E950.

Research output: Contribution to journalArticle

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
Larsson SC, Traylor M, Burgess S, Boncoraglio GB, Jern C, Michaëlsson K et al. Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study. Neurology. 2019 Feb 26;92(9):E944-E950. https://doi.org/10.1212/WNL.0000000000007001
Larsson, Susanna C. ; Traylor, Matthew ; Burgess, Stephen ; Boncoraglio, Giorgio B. ; Jern, Christina ; Michaëlsson, Karl ; Markus, Hugh S. ; Malik, Rainer ; Chauhan, Ganesh ; Sargurupremraj, Muralidharan ; Okada, Yukinori ; Mishra, Aniket ; Rutten-Jacobs, Loes ; Giese, Anne Katrin ; Van Der Laan, Sander W. ; Gretarsdottir, Solveig ; Anderson, Christopher D. ; Chong, Michael ; Adams, Hieab H.H. ; Ago, Tetsuro ; Almgren, Peter ; Amouyel, Philippe ; Ay, Hakan ; Bartz, Raci M. ; Benavente, Oscar R. ; Bevan, Steve ; Brown, Robert D. ; Butterworth, Adam S. ; Carrera, Caty ; Carty, Cara L. ; Chasman, Daniel I. ; Chen, Wei Min ; Cole, John W. ; Correa, Adolfo ; Cotlarciuc, Ioana ; Cruchaga, Carlos ; Danesh, John ; De Bakker, Paul I.W. ; Destefano, Anita L. ; Hoed, Marcel Den ; Duan, Qing ; Engelter, Stefan T. ; Falcone, Guido J. ; Gottesman, Rebecca F. ; Grewal, Raji P. ; Gudnason, Vilmundur ; Gustafsson, Stefan ; Haessler, Jeffrey ; Harris, Tamara B. ; Hassan, Ahamad ; Havulinna, Aki S. ; Heckbert, Susan R. ; Holliday, Elizabeth G. ; Howard, George ; Hsu, Fang Chi ; Hyacinth, Hyacinth I. ; Ikram, M. Arfan ; Ingelsson, Erik ; Irvin, Marguerite R. ; Jian, Xueqiu ; Jiménez-Conde, Jordi ; Johnson, Julie A. ; Jukema, J. Wouter ; Kanai, Masahiro ; Keene, Keith L. ; Kissela, Brett M. ; Kleindorfer, Dawn O. ; Kooperberg, Charles ; Kubo, Michiaki ; Lange, Leslie A. ; Langefeld, Carl D. ; Langenberg, Claudia ; Launer, Lenore J. ; Lee, Jin Moo ; Lemmens, Robin ; Leys, Didier ; Lewis, Cathryn M. ; Lin, Wei Yu ; Lindgren, Arne G. ; Lorentzen, Erik ; Magnusson, Patrik K. ; Maguire, Jane ; Manichaikul, Ani ; McArdle, Patrick F. ; Meschia, James F. ; Mitchell, Braxton D. ; Mosley, Thomas H. ; Nalls, Michael A. ; Ninomiya, Toshiharu ; O'Donnell, Martin J. ; Psaty, Bruce M. ; Pulit, Sara L. ; Rannikmäe, Kristiina ; Reiner, Alexander P. ; Rexrode, Kathryn M. ; Rice, Kenneth ; Rich, Stephen S. ; Ridker, Paul M. ; Rost, Natalia S. ; Rothwell, Peter M. ; Rotter, Jerome I. ; Rundek, Tatjana ; Sacco, Ralph L. ; Sakaue, Saori ; Sale, Michele M. ; Salomaa, Veikko ; Sapkota, Bishwa R. ; Schmidt, Reinhold ; Schmidt, Carsten O. ; Schminke, Ulf ; Sharma, Pankaj ; Slowik, Agnieszka ; Sudlow, Cathie L.M. ; Tanislav, Christian ; Tatlisumak, Turgut ; Taylor, Kent D. ; Thijs, Vincent N.S. ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Tiedt, Steffen ; Trompet, Stella ; Tzourio, Christophe ; Van Duijn, Cornelia M. ; Walters, Matthew ; Wareham, Nicholas J. ; Wassertheil-Smoller, Sylvia ; Wilson, James G. ; Wiggins, Kerri L. ; Yang, Qiong ; Yusuf, Salim ; Amin, Najaf ; Aparicio, Hugo S. ; Arnett, Donna K. ; Attia, John ; Beiser, Alexa S. ; Berr, Claudine ; Buring, Julie E. ; Bustamante, Mariana ; Caso, Valeria ; Cheng, Yu Ching ; Choi, Seung Hoan ; Chowhan, Ayesha ; Cullell, Natalia ; Dartigues, Jean François ; Delavaran, Hossein ; Delgado, Pilar ; Dörr, Marcus ; Engström, Gunnar ; Ford, Ian ; Gurpreet, Wander S. ; Hamsten, Anders ; Heitsch, Laura ; Hozawa, Atsushi ; Ibanez, Laura ; Ilinca, Andreea ; Ingelsson, Martin ; Iwasaki, Motoki ; Jackson, Rebecca D. ; Jood, Katarina ; Jousilahti, Pekka ; Kaffashian, Sara ; Kalra, Lalit ; Kamouchi, Masahiro ; Kitazono, Takanari ; Kjartansson, Olafur ; Kloss, Manja ; Koudstaal, Peter J. ; Krupinski, Jerzy ; Labovitz, Daniel L. ; Laurie, Cathy C. ; Levi, Christopher R. ; Li, Linxin ; Lind, Lars ; Lindgren, Cecilia M. ; Lioutas, Vasileios ; Liu, Yong Mei ; Lopez, Oscar L. ; Makoto, Hirata ; Martinez-Majander, Nicolas ; Matsuda, Koichi ; Minegishi, Naoko ; Montaner, Joan ; Morris, Andrew P. ; Muiño, Elena ; Müller-Nurasyid, Martina ; Norrving, Bo ; Ogishima, Soichi ; Parati, Eugenio A. ; Peddareddygari, Leema Reddy ; Pedersen, Nancy L. ; Pera, Joanna ; Perola, Markus ; Pezzini, Alessandro ; Pileggi, Silvana ; Rabionet, Raquel ; Riba-Llena, Iolanda ; Ribasés, Marta ; Romero, Jose R. ; Roquer, Jaume ; Rudd, Anthony G. ; Sarin, Antti Pekka ; Sarju, Ralhan ; Sarnowski, Chloe ; Sasaki, Makoto ; Satizabal, Claudia L. ; Satoh, Mamoru ; Sattar, Naveed ; Sawada, Norie ; Sibolt, Gerli ; Sigurdsson, Ásgeir ; Smith, Albert ; Sobue, Kenji ; Soriano-Tárraga, Carolina ; Stanne, Tara ; Stine, O. Colin ; Stott, David J. ; Strauch, Konstantin ; Takai, Takako ; Tanaka, Hideo ; Tanno, Kozo ; Teumer, Alexander ; Tomppo, Liisa ; Torres-Aguila, Nuria P. ; Touze, Emmanuel ; Tsugane, Shoichiro ; Uitterlinden, Andre G. ; Valdimarsson, Einar M. ; Van Der Lee, Sven J. ; Völzke, Henry ; Wakai, Kenji ; Weir, David ; Williams, Stephen R. ; Wolfe, Charles D.A. ; Wong, Quenna ; Xu, Huichun ; Yamaji, Taiki ; Sanghera, Dharambir K. ; Melander, Olle ; Strbian, Daniel ; Fernandez-Cadenas, Israel ; Longstreth, W. T. ; Rolfs, Arndt ; Hata, Jun ; Woo, Daniel ; Rosand, Jonathan ; Pare, Guillaume ; Hopewell, Jemma C. ; Saleheen, Danish ; Stefansson, Kari ; Worrall, Bradford B. ; Kittner, Steven J. ; Seshadri, Sudha ; Fornage, Myriam ; Howson, Joanna M.M. ; Kamatani, Yoichiro ; Debette, Stephanie ; Dichgans, Martin. / Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study. In: Neurology. 2019 ; Vol. 92, No. 9. pp. E944-E950.
@article{cabafe8ec2054fe2918bbc46ba8293c7,
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{\cc}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",
year = "2019",
month = "2",
day = "26",
doi = "10.1212/WNL.0000000000007001",
language = "English",
volume = "92",
pages = "E944--E950",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

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

AU - Boncoraglio, Giorgio B.

AU - Jern, Christina

AU - Michaëlsson, Karl

AU - Markus, Hugh S.

AU - Malik, Rainer

AU - Chauhan, Ganesh

AU - Sargurupremraj, Muralidharan

AU - Okada, Yukinori

AU - Mishra, Aniket

AU - Rutten-Jacobs, Loes

AU - Giese, Anne Katrin

AU - Van Der Laan, Sander W.

AU - Gretarsdottir, Solveig

AU - Anderson, Christopher D.

AU - Chong, Michael

AU - Adams, Hieab H.H.

AU - Ago, Tetsuro

AU - Almgren, Peter

AU - Amouyel, Philippe

AU - Ay, Hakan

AU - Bartz, Raci M.

AU - Benavente, Oscar R.

AU - Bevan, Steve

AU - Brown, Robert D.

AU - Butterworth, Adam S.

AU - Carrera, Caty

AU - Carty, Cara L.

AU - Chasman, Daniel I.

AU - Chen, Wei Min

AU - Cole, John W.

AU - Correa, Adolfo

AU - Cotlarciuc, Ioana

AU - Cruchaga, Carlos

AU - Danesh, John

AU - De Bakker, Paul I.W.

AU - Destefano, Anita L.

AU - Hoed, Marcel Den

AU - Duan, Qing

AU - Engelter, Stefan T.

AU - Falcone, Guido J.

AU - Gottesman, Rebecca F.

AU - Grewal, Raji P.

AU - Gudnason, Vilmundur

AU - Gustafsson, Stefan

AU - Haessler, Jeffrey

AU - Harris, Tamara B.

AU - Hassan, Ahamad

AU - Havulinna, Aki S.

AU - Heckbert, Susan R.

AU - Holliday, Elizabeth G.

AU - Howard, George

AU - Hsu, Fang Chi

AU - Hyacinth, Hyacinth I.

AU - Ikram, M. Arfan

AU - Ingelsson, Erik

AU - Irvin, Marguerite R.

AU - Jian, Xueqiu

AU - Jiménez-Conde, Jordi

AU - Johnson, Julie A.

AU - Jukema, J. Wouter

AU - Kanai, Masahiro

AU - Keene, Keith L.

AU - Kissela, Brett M.

AU - Kleindorfer, Dawn O.

AU - Kooperberg, Charles

AU - Kubo, Michiaki

AU - Lange, Leslie A.

AU - Langefeld, Carl D.

AU - Langenberg, Claudia

AU - Launer, Lenore J.

AU - Lee, Jin Moo

AU - Lemmens, Robin

AU - Leys, Didier

AU - Lewis, Cathryn M.

AU - Lin, Wei Yu

AU - Lindgren, Arne G.

AU - Lorentzen, Erik

AU - Magnusson, Patrik K.

AU - Maguire, Jane

AU - Manichaikul, Ani

AU - McArdle, Patrick F.

AU - Meschia, James F.

AU - Mitchell, Braxton D.

AU - Mosley, Thomas H.

AU - Nalls, Michael A.

AU - Ninomiya, Toshiharu

AU - O'Donnell, Martin J.

AU - Psaty, Bruce M.

AU - Pulit, Sara L.

AU - Rannikmäe, Kristiina

AU - Reiner, Alexander P.

AU - Rexrode, Kathryn M.

AU - Rice, Kenneth

AU - Rich, Stephen S.

AU - Ridker, Paul M.

AU - Rost, Natalia S.

AU - Rothwell, Peter M.

AU - Rotter, Jerome I.

AU - Rundek, Tatjana

AU - Sacco, Ralph L.

AU - Sakaue, Saori

AU - Sale, Michele M.

AU - Salomaa, Veikko

AU - Sapkota, Bishwa R.

AU - Schmidt, Reinhold

AU - Schmidt, Carsten O.

AU - Schminke, Ulf

AU - Sharma, Pankaj

AU - Slowik, Agnieszka

AU - Sudlow, Cathie L.M.

AU - Tanislav, Christian

AU - Tatlisumak, Turgut

AU - Taylor, Kent D.

AU - Thijs, Vincent N.S.

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Tiedt, Steffen

AU - Trompet, Stella

AU - Tzourio, Christophe

AU - Van Duijn, Cornelia M.

AU - Walters, Matthew

AU - Wareham, Nicholas J.

AU - Wassertheil-Smoller, Sylvia

AU - Wilson, James G.

AU - Wiggins, Kerri L.

AU - Yang, Qiong

AU - Yusuf, Salim

AU - Amin, Najaf

AU - Aparicio, Hugo S.

AU - Arnett, Donna K.

AU - Attia, John

AU - Beiser, Alexa S.

AU - Berr, Claudine

AU - Buring, Julie E.

AU - Bustamante, Mariana

AU - Caso, Valeria

AU - Cheng, Yu Ching

AU - Choi, Seung Hoan

AU - Chowhan, Ayesha

AU - Cullell, Natalia

AU - Dartigues, Jean François

AU - Delavaran, Hossein

AU - Delgado, Pilar

AU - Dörr, Marcus

AU - Engström, Gunnar

AU - Ford, Ian

AU - Gurpreet, Wander S.

AU - Hamsten, Anders

AU - Heitsch, Laura

AU - Hozawa, Atsushi

AU - Ibanez, Laura

AU - Ilinca, Andreea

AU - Ingelsson, Martin

AU - Iwasaki, Motoki

AU - Jackson, Rebecca D.

AU - Jood, Katarina

AU - Jousilahti, Pekka

AU - Kaffashian, Sara

AU - Kalra, Lalit

AU - Kamouchi, Masahiro

AU - Kitazono, Takanari

AU - Kjartansson, Olafur

AU - Kloss, Manja

AU - Koudstaal, Peter J.

AU - Krupinski, Jerzy

AU - Labovitz, Daniel L.

AU - Laurie, Cathy C.

AU - Levi, Christopher R.

AU - Li, Linxin

AU - Lind, Lars

AU - Lindgren, Cecilia M.

AU - Lioutas, Vasileios

AU - Liu, Yong Mei

AU - Lopez, Oscar L.

AU - Makoto, Hirata

AU - Martinez-Majander, Nicolas

AU - Matsuda, Koichi

AU - Minegishi, Naoko

AU - Montaner, Joan

AU - Morris, Andrew P.

AU - Muiño, Elena

AU - Müller-Nurasyid, Martina

AU - Norrving, Bo

AU - Ogishima, Soichi

AU - Parati, Eugenio A.

AU - Peddareddygari, Leema Reddy

AU - Pedersen, Nancy L.

AU - Pera, Joanna

AU - Perola, Markus

AU - Pezzini, Alessandro

AU - Pileggi, Silvana

AU - Rabionet, Raquel

AU - Riba-Llena, Iolanda

AU - Ribasés, Marta

AU - Romero, Jose R.

AU - Roquer, Jaume

AU - Rudd, Anthony G.

AU - Sarin, Antti Pekka

AU - Sarju, Ralhan

AU - Sarnowski, Chloe

AU - Sasaki, Makoto

AU - Satizabal, Claudia L.

AU - Satoh, Mamoru

AU - Sattar, Naveed

AU - Sawada, Norie

AU - Sibolt, Gerli

AU - Sigurdsson, Ásgeir

AU - Smith, Albert

AU - Sobue, Kenji

AU - Soriano-Tárraga, Carolina

AU - Stanne, Tara

AU - Stine, O. Colin

AU - Stott, David J.

AU - Strauch, Konstantin

AU - Takai, Takako

AU - Tanaka, Hideo

AU - Tanno, Kozo

AU - Teumer, Alexander

AU - Tomppo, Liisa

AU - Torres-Aguila, Nuria P.

AU - Touze, Emmanuel

AU - Tsugane, Shoichiro

AU - Uitterlinden, Andre G.

AU - Valdimarsson, Einar M.

AU - Van Der Lee, Sven J.

AU - Völzke, Henry

AU - Wakai, Kenji

AU - Weir, David

AU - Williams, Stephen R.

AU - Wolfe, Charles D.A.

AU - Wong, Quenna

AU - Xu, Huichun

AU - Yamaji, Taiki

AU - Sanghera, Dharambir K.

AU - Melander, Olle

AU - Strbian, Daniel

AU - Fernandez-Cadenas, Israel

AU - Longstreth, W. T.

AU - Rolfs, Arndt

AU - Hata, Jun

AU - Woo, Daniel

AU - Rosand, Jonathan

AU - Pare, Guillaume

AU - Hopewell, Jemma C.

AU - Saleheen, Danish

AU - Stefansson, Kari

AU - Worrall, Bradford B.

AU - Kittner, Steven J.

AU - Seshadri, Sudha

AU - Fornage, Myriam

AU - Howson, Joanna M.M.

AU - Kamatani, Yoichiro

AU - Debette, Stephanie

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

VL - 92

SP - E944-E950

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 9

ER -