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

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Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. / Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G; Terwindt, Gisela M; Sturm, Jonathan; Bis, Joshua C; Hopewell, Jemma C; Ferrari, Michel D; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I; Mitchell, Braxton D; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T; Kurth, Tobias; Ikram, M Arfan; Reiner, Alex P; Longstreth, W T; Rothwell, Peter M; Strachan, David P; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B; Davey Smith, George; van Duijn, Cornelia M; Stefansson, Kari; Worrall, Bradford B; Nyholt, Dale R; Markus, Hugh S; van den Maagdenberg, Arn M J M; Cotsapas, Chris; Zwart, John A; Palotie, Aarno; Dichgans, Martin; International Headache Genetics Consortium.

In: NEUROLOGY, Vol. 84, No. 21, 26.05.2015, p. 2132-45.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Malik, R, Freilinger, T, Winsvold, BS, Anttila, V, Vander 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, Ikram, MA, Reiner, AP, Longstreth, WT, 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, Dichgans, M & International Headache Genetics Consortium 2015, 'Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants', NEUROLOGY, vol. 84, no. 21, pp. 2132-45. https://doi.org/10.1212/WNL.0000000000001606

APA

Malik, R., Freilinger, T., Winsvold, B. S., Anttila, V., Vander 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., ... International Headache Genetics Consortium (2015). Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. NEUROLOGY, 84(21), 2132-45. https://doi.org/10.1212/WNL.0000000000001606

Vancouver

Malik R, Freilinger T, Winsvold BS, Anttila V, Vander Heiden J, Traylor M et al. Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. NEUROLOGY. 2015 May 26;84(21):2132-45. https://doi.org/10.1212/WNL.0000000000001606

Bibtex

@article{e7e6cc32135d46499730a27af470bbdc,
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.",
keywords = "Brain Ischemia, Genome-Wide Association Study, Humans, Migraine with Aura, Migraine without Aura, Stroke",
author = "Rainer Malik and Tobias Freilinger and Winsvold, {Bendik S} and Verneri Anttila and {Vander Heiden}, Jason and Matthew Traylor and {de Vries}, Boukje and Holliday, {Elizabeth G} and Terwindt, {Gisela M} and Jonathan Sturm and Bis, {Joshua C} and Hopewell, {Jemma C} and Ferrari, {Michel D} and Kristiina Rannikmae and Maija Wessman and Mikko Kallela and Christian Kubisch and Myriam Fornage and Meschia, {James F} and Terho Lehtim{\"a}ki and Cathie Sudlow and Robert Clarke and Chasman, {Daniel I} and Mitchell, {Braxton D} and Jane Maguire and Jaakko Kaprio and Martin Farrall and Raitakari, {Olli T} and Tobias Kurth and Ikram, {M Arfan} and Reiner, {Alex P} and Longstreth, {W T} and Rothwell, {Peter M} and Strachan, {David P} and Pankaj Sharma and Sudha Seshadri and Lydia Quaye and Lynn Cherkas and Markus Sch{\"u}rks and Jonathan Rosand and Lannie Ligthart and Boncoraglio, {Giorgio B} and {Davey Smith}, George and {van Duijn}, {Cornelia M} and Kari Stefansson and Worrall, {Bradford B} and Nyholt, {Dale R} and Markus, {Hugh S} and {van den Maagdenberg}, {Arn M J M} and Chris Cotsapas and Zwart, {John A} and Aarno Palotie and Martin Dichgans and {International Headache Genetics Consortium}",
note = "{\textcopyright} 2015 American Academy of Neurology.",
year = "2015",
month = may,
day = "26",
doi = "10.1212/WNL.0000000000001606",
language = "English",
volume = "84",
pages = "2132--45",
journal = "NEUROLOGY",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "21",

}

RIS

TY - JOUR

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

AU - Malik, Rainer

AU - Freilinger, Tobias

AU - Winsvold, Bendik S

AU - Anttila, Verneri

AU - Vander Heiden, Jason

AU - Traylor, Matthew

AU - de Vries, Boukje

AU - Holliday, Elizabeth G

AU - Terwindt, Gisela M

AU - Sturm, Jonathan

AU - Bis, Joshua C

AU - Hopewell, Jemma C

AU - Ferrari, Michel D

AU - Rannikmae, Kristiina

AU - Wessman, Maija

AU - Kallela, Mikko

AU - Kubisch, Christian

AU - Fornage, Myriam

AU - Meschia, James F

AU - Lehtimäki, Terho

AU - Sudlow, Cathie

AU - Clarke, Robert

AU - Chasman, Daniel I

AU - Mitchell, Braxton D

AU - Maguire, Jane

AU - Kaprio, Jaakko

AU - Farrall, Martin

AU - Raitakari, Olli T

AU - Kurth, Tobias

AU - Ikram, M Arfan

AU - Reiner, Alex P

AU - Longstreth, W T

AU - Rothwell, Peter M

AU - Strachan, David P

AU - Sharma, Pankaj

AU - Seshadri, Sudha

AU - Quaye, Lydia

AU - Cherkas, Lynn

AU - Schürks, Markus

AU - Rosand, Jonathan

AU - Ligthart, Lannie

AU - Boncoraglio, Giorgio B

AU - Davey Smith, George

AU - van Duijn, Cornelia M

AU - Stefansson, Kari

AU - Worrall, Bradford B

AU - Nyholt, Dale R

AU - Markus, Hugh S

AU - van den Maagdenberg, Arn M J M

AU - Cotsapas, Chris

AU - Zwart, John A

AU - Palotie, Aarno

AU - Dichgans, Martin

AU - International Headache Genetics Consortium

N1 - © 2015 American Academy of Neurology.

PY - 2015/5/26

Y1 - 2015/5/26

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.

KW - Brain Ischemia

KW - Genome-Wide Association Study

KW - Humans

KW - Migraine with Aura

KW - Migraine without Aura

KW - Stroke

U2 - 10.1212/WNL.0000000000001606

DO - 10.1212/WNL.0000000000001606

M3 - SCORING: Journal article

C2 - 25934857

VL - 84

SP - 2132

EP - 2145

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 21

ER -