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

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., Lehtimaki, T., Sudlow, C., Clarke, R., Chasman, D.I., Mitchell, B.D., Maguire, J., Kaprio, J., Farrall, M., Raitakari, O.T., Kurth, T., Ikram, M.A., Reiner, A.P., Longstreth, W.T., Rothwell, P.M., Strachan, D.P., Sharma, P., Seshadri, S., Quaye, L., Cherkas, L., Schurks, M., Rosand, J., Ligthart, L., Boncoraglio, G.B., Davey Smith, G., van Duijn, C.M., Stefansson, K., Worrall, B.B., Nyholt, D.R., Markus, H.S., van den Maagdenberg, A.M., Cotsapas, C., Zwart, J.A., Palotie, A., & Dichgans, M. (2015) Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. Neurology, 84(21), pp. 2132-2145.

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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 x 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 x 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.

Impact and interest:

22 citations in Scopus
22 citations in Web of Science®
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ID Code: 91781
Item Type: Journal Article
Refereed: Yes
Additional Information: For the METASTROKE Collaboration of the International Stroke Genetics Consortium
Keywords: Brain Ischemia/epidemiology/*genetics, *Genome-Wide Association Study, Humans, Migraine with Aura/epidemiology/*genetics, Migraine without Aura/epidemiology/*genetics, Stroke/epidemiology/*genetics
DOI: 10.1212/WNL.0000000000001606
ISSN: 1526-632X
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 12 Jan 2016 04:36
Last Modified: 13 Jan 2016 02:31

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