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

S.C. Larsson; M. Traylor; S. Burgess; G.B. Boncoraglio; C. Jern; K. Michaëlsson; H.S. Markus; R. Malik; G. Chauhan; M. Sargurupremraj; Y. Okada; A. Mishra; L. Rutten-Jacobs; A.-K. Giese; S. W. van der Laan; S. Gretarsdottir; C.D. Anderson; M. Chong; H.H.H. Adams; T. Ago; P. Almgren; P. Amouyel; H. Ay; R.M. Bartz; O.R. Benavente; S. Bevan; R.D. Brown; A.S. Butterworth; C. Carrera; C.L. Carty; D.I. Chasman; W.-M. Chen; J.W. Cole; A. Correa; I. Cotlarciuc; C. Cruchaga; J. Danesh; P.IW. De Bakker; A.L. Destefano; M.D. Hoed; Q. Duan; S.T. Engelter; G.J. Falcone; R.F. Gottesman; R.P. Grewal; V. Gudnason; S. Gustafsson; J. Haessler; T.B. Harris; A. Hassan; A.S. Havulinna; C.R. Levi; null et al.

doi:10.1212/WNL.0000000000007001

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

S.C. Larsson, M. Traylor, S. Burgess, G.B. Boncoraglio, C. Jern, K. Michaëlsson, H.S. Markus, R. Malik, G. Chauhan, M. Sargurupremraj, Y. Okada, A. Mishra, L. Rutten-Jacobs, A.-K. Giese, S. W. van der Laan, S. Gretarsdottir, C.D. Anderson, M. Chong, H.H.H. Adams, T. AgoP. Almgren, P. Amouyel, H. Ay, R.M. Bartz, O.R. Benavente, S. Bevan, R.D. Brown, A.S. Butterworth, C. Carrera, C.L. Carty, D.I. Chasman, W.-M. Chen, J.W. Cole, A. Correa, I. Cotlarciuc, C. Cruchaga, J. Danesh, P.IW. De Bakker, A.L. Destefano, M.D. Hoed, Q. Duan, S.T. Engelter, G.J. Falcone, R.F. Gottesman, R.P. Grewal, V. Gudnason, S. Gustafsson, J. Haessler, T.B. Harris, A. Hassan, A.S. Havulinna, C.R. Levi, et al.

Western Sydney University

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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
Number of pages	7
Journal	Neurology
Volume	92
Issue number	9
DOIs	https://doi.org/10.1212/WNL.0000000000007001
Publication status	Published - 2019

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This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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10.1212/WNL.0000000000007001

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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., ... et al. (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{803bbd1117924849bed9f49c64039a85,

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 = "S.C. Larsson and M. Traylor and S. Burgess and G.B. Boncoraglio and C. Jern and K. Micha{\"e}lsson and H.S. Markus and R. Malik and G. Chauhan and M. Sargurupremraj and Y. Okada and A. Mishra and L. Rutten-Jacobs and A.-K. Giese and {van der Laan}, {S. W.} and S. Gretarsdottir and C.D. Anderson and M. Chong and H.H.H. Adams and T. Ago and P. Almgren and P. Amouyel and H. Ay and R.M. Bartz and O.R. Benavente and S. Bevan and R.D. Brown and A.S. Butterworth and C. Carrera and C.L. Carty and D.I. Chasman and W.-M. Chen and J.W. Cole and A. Correa and I. Cotlarciuc and C. Cruchaga and J. Danesh and {De Bakker}, P.IW. and A.L. Destefano and M.D. Hoed and Q. Duan and S.T. Engelter and G.J. Falcone and R.F. Gottesman and R.P. Grewal and V. Gudnason and S. Gustafsson and J. Haessler and T.B. Harris and A. Hassan and A.S. Havulinna and C.R. Levi and {et al.}",

year = "2019",

doi = "10.1212/WNL.0000000000007001",

language = "English",

volume = "92",

pages = "E944--E950",

journal = "Neurology",

issn = "0028-3878",

publisher = "Wolters Kluwer Health",

number = "9",

}

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, A-K, 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, W-M, 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, Levi, CR & et al. 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 : Mendelian randomization study

AU - Larsson, S.C.

AU - Traylor, M.

AU - Burgess, S.

AU - Boncoraglio, G.B.

AU - Jern, C.

AU - Michaëlsson, K.

AU - Markus, H.S.

AU - Malik, R.

AU - Chauhan, G.

AU - Sargurupremraj, M.

AU - Okada, Y.

AU - Mishra, A.

AU - Rutten-Jacobs, L.

AU - Giese, A.-K.

AU - van der Laan, S. W.

AU - Gretarsdottir, S.

AU - Anderson, C.D.

AU - Chong, M.

AU - Adams, H.H.H.

AU - Ago, T.

AU - Almgren, P.

AU - Amouyel, P.

AU - Ay, H.

AU - Bartz, R.M.

AU - Benavente, O.R.

AU - Bevan, S.

AU - Brown, R.D.

AU - Butterworth, A.S.

AU - Carrera, C.

AU - Carty, C.L.

AU - Chasman, D.I.

AU - Chen, W.-M.

AU - Cole, J.W.

AU - Correa, A.

AU - Cotlarciuc, I.

AU - Cruchaga, C.

AU - Danesh, J.

AU - De Bakker, P.IW.

AU - Destefano, A.L.

AU - Hoed, M.D.

AU - Duan, Q.

AU - Engelter, S.T.

AU - Falcone, G.J.

AU - Gottesman, R.F.

AU - Grewal, R.P.

AU - Gudnason, V.

AU - Gustafsson, S.

AU - Haessler, J.

AU - Harris, T.B.

AU - Hassan, A.

AU - Havulinna, A.S.

AU - Levi, C.R.

AU - et al., null

PY - 2019

Y1 - 2019

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://hdl.handle.net/1959.7/uws:67011

U2 - 10.1212/WNL.0000000000007001

DO - 10.1212/WNL.0000000000007001

M3 - Article

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

Abstract

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