Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants

R. Malik; T. Freilinger; B.S. Winsvold; V. Anttila; J. van der Heiden; M. Traylor; B. de Vries; E.G. Holliday; G.M. Terwindt; J. Sturm; J.C. Bis; J.C. Hopewell; M.D. Ferrari; K. Rannikmae; M. Wessman; M. Kallela; C. Kubisch; M. Fornage; J.F. Meschia; T. Lehtimäki; C. Sudlow; R. Clarke; D.I. Chasman; B.D. Mitchell; J. Maguire; J. Kaprio; M. Farrall; O.T. Raitakari; T. Kurth; M. Arfan Ikram; A.P. Reiner; Jr. W.T. Longstreth; P.M. Rothwell; D.P. Strachan; P. Sharma; S. Seshadri; L. Quaye; L. Cherkas; M. Schürks; J. Rosand; L. Ligthart; G.B. Boncoraglio; G. Davey Smith; C.M. van Duijn; K. Stefansson; B.B. Worrall; DR Nyholt; H.S. Markus; A.M.J.M. van den Maagdenberg; C. Cotsapas; J.A. Zwart; A. Palotie

doi:10.1212/WNL.0000000000001606

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants

R. Malik, T. Freilinger, B.S. Winsvold, V. Anttila, J. van der Heiden, M. Traylor, B. de Vries, E.G. Holliday, G.M. Terwindt, J. Sturm, J.C. Bis, J.C. Hopewell, M.D. Ferrari, K. Rannikmae, M. Wessman, M. Kallela, C. Kubisch, M. Fornage, J.F. Meschia, T. LehtimäkiC. Sudlow, R. Clarke, D.I. Chasman, B.D. Mitchell, J. Maguire, J. Kaprio, M. Farrall, O.T. Raitakari, T. Kurth, M. Arfan Ikram, A.P. Reiner, Jr. W.T. Longstreth, P.M. Rothwell, D.P. Strachan, P. Sharma, S. Seshadri, L. Quaye, L. Cherkas, M. Schürks, J. Rosand, L. Ligthart, G.B. Boncoraglio, G. Davey Smith, C.M. van Duijn, K. Stefansson, B.B. Worrall, DR Nyholt, H.S. Markus, A.M.J.M. van den Maagdenberg, C. Cotsapas, J.A. Zwart, A. Palotie

Biological Psychology

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p 6.4 × 10-28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p 2.7 × 10-20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

Original language	English
Pages (from-to)	2132-2145
Journal	Neurology
Volume	84
Issue number	21
DOIs	https://doi.org/10.1212/WNL.0000000000001606
Publication status	Published - 2015

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10.1212/WNL.0000000000001606

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Malik, R., Freilinger, T., Winsvold, B. S., Anttila, V., van der Heiden, J., Traylor, M., de Vries, B., Holliday, E. G., Terwindt, G. M., Sturm, J., Bis, J. C., Hopewell, J. C., Ferrari, M. D., Rannikmae, K., Wessman, M., Kallela, M., Kubisch, C., Fornage, M., Meschia, J. F., ... Palotie, A. (2015). Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. Neurology, 84(21), 2132-2145. https://doi.org/10.1212/WNL.0000000000001606

@article{1d651142e64948738e64788e7e612bd9,

title = "Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants",

abstract = "Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p 6.4 × 10-28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p 2.7 × 10-20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.",

author = "R. Malik and T. Freilinger and B.S. Winsvold and V. Anttila and {van der Heiden}, J. and M. Traylor and {de Vries}, B. and E.G. Holliday and G.M. Terwindt and J. Sturm and J.C. Bis and J.C. Hopewell and M.D. Ferrari and K. Rannikmae and M. Wessman and M. Kallela and C. Kubisch and M. Fornage and J.F. Meschia and T. Lehtim{\"a}ki and C. Sudlow and R. Clarke and D.I. Chasman and B.D. Mitchell and J. Maguire and J. Kaprio and M. Farrall and O.T. Raitakari and T. Kurth and {Arfan Ikram}, M. and A.P. Reiner and Longstreth, {Jr. W.T.} and P.M. Rothwell and D.P. Strachan and P. Sharma and S. Seshadri and L. Quaye and L. Cherkas and M. Sch{\"u}rks and J. Rosand and L. Ligthart and G.B. Boncoraglio and {Davey Smith}, G. and {van Duijn}, C.M. and K. Stefansson and B.B. Worrall and DR Nyholt and H.S. Markus and {van den Maagdenberg}, A.M.J.M. and C. Cotsapas and J.A. Zwart and A. Palotie",

year = "2015",

doi = "10.1212/WNL.0000000000001606",

language = "English",

volume = "84",

pages = "2132--2145",

journal = "Neurology",

issn = "0028-3878",

publisher = "American Academy of Neurology",

number = "21",

}

Malik, R, Freilinger, T, Winsvold, BS, Anttila, V, van der Heiden, J, Traylor, M, de Vries, B, Holliday, EG, Terwindt, GM, Sturm, J, Bis, JC, Hopewell, JC, Ferrari, MD, Rannikmae, K, Wessman, M, Kallela, M, Kubisch, C, Fornage, M, Meschia, JF, Lehtimäki, T, Sudlow, C, Clarke, R, Chasman, DI, Mitchell, BD, Maguire, J, Kaprio, J, Farrall, M, Raitakari, OT, Kurth, T, Arfan Ikram, M, Reiner, AP, Longstreth, JWT, Rothwell, PM, Strachan, DP, Sharma, P, Seshadri, S, Quaye, L, Cherkas, L, Schürks, M, Rosand, J, Ligthart, L, Boncoraglio, GB, Davey Smith, G, van Duijn, CM, Stefansson, K, Worrall, BB, Nyholt, DR, Markus, HS, van den Maagdenberg, AMJM, Cotsapas, C, Zwart, JA & Palotie, A 2015, 'Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants', Neurology, vol. 84, no. 21, pp. 2132-2145. https://doi.org/10.1212/WNL.0000000000001606

TY - JOUR

T1 - Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants

AU - Malik, R.

AU - Freilinger, T.

AU - Winsvold, B.S.

AU - Anttila, V.

AU - van der Heiden, J.

AU - Traylor, M.

AU - de Vries, B.

AU - Holliday, E.G.

AU - Terwindt, G.M.

AU - Sturm, J.

AU - Bis, J.C.

AU - Hopewell, J.C.

AU - Ferrari, M.D.

AU - Rannikmae, K.

AU - Wessman, M.

AU - Kallela, M.

AU - Kubisch, C.

AU - Fornage, M.

AU - Meschia, J.F.

AU - Lehtimäki, T.

AU - Sudlow, C.

AU - Clarke, R.

AU - Chasman, D.I.

AU - Mitchell, B.D.

AU - Maguire, J.

AU - Kaprio, J.

AU - Farrall, M.

AU - Raitakari, O.T.

AU - Kurth, T.

AU - Arfan Ikram, M.

AU - Reiner, A.P.

AU - Longstreth, Jr. W.T.

AU - Rothwell, P.M.

AU - Strachan, D.P.

AU - Sharma, P.

AU - Seshadri, S.

AU - Quaye, L.

AU - Cherkas, L.

AU - Schürks, M.

AU - Rosand, J.

AU - Ligthart, L.

AU - Boncoraglio, G.B.

AU - Davey Smith, G.

AU - van Duijn, C.M.

AU - Stefansson, K.

AU - Worrall, B.B.

AU - Nyholt, DR

AU - Markus, H.S.

AU - van den Maagdenberg, A.M.J.M.

AU - Cotsapas, C.

AU - Zwart, J.A.

AU - Palotie, A.

PY - 2015

Y1 - 2015

N2 - Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p 6.4 × 10-28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p 2.7 × 10-20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

AB - Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p 6.4 × 10-28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p 2.7 × 10-20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

U2 - 10.1212/WNL.0000000000001606

DO - 10.1212/WNL.0000000000001606

M3 - Article

SN - 0028-3878

VL - 84

SP - 2132

EP - 2145

JO - Neurology

JF - Neurology

IS - 21

ER -

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants

Abstract

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