Genetic analysis for a shared biological basis between migraine and coronary artery disease


Autoria(s): Winsvold, B. S.; Nelson, C. P.; Malik, R.; Gormley, P.; Anttila, V.; Vander Heiden, J.; Elliott, K. S.; Jacobsen, L. M.; Palta, P.; Amin, N.; de Vries, B.; Hamalainen, E.; Freilinger, T.; Ikram, M. A.; Kessler, T.; Koiranen, M.; Ligthart, L.; McMahon, G.; Pedersen, L. M.; Willenborg, C.; Won, H.-H.; Olesen, J.; Artto, V.; Assimes, T. L.; Blankenberg, S.; Boomsma, D. I.; Cherkas, L.; Davey Smith, G.; Epstein, S. E.; Erdmann, J.; Ferrari, M. D.; Gobel, H.; Hall, A. S.; Jarvelin, M.-R.; Kallela, M.; Kaprio, J.; Kathiresan, S.; Lehtimaki, T.; McPherson, R.; Marz, W.; Nyholt, D.R.; O'Donnell, C. J.; Quaye, L.; Rader, D. J.; Raitakari, O.; Roberts, R.; Schunkert, H.; Schurks, M.; Stewart, A. F. R.; Terwindt, G. M.; Thorsteinsdottir, U.; van den Maagdenberg, A. M. J. M.; van Duijn, C.; Wessman, M.; Kurth, T.; Kubisch, C.; Dichgans, M.; Chasman, D. I.; Cotsapas, C.; Zwart, J.-A.; Samani, N. J.; Palotie, A.
Data(s)

01/06/2015

Resumo

Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

Formato

application/pdf

application/zip

Identificador

http://eprints.qut.edu.au/91754/

Publicador

American Academy of Neurology

Relação

http://eprints.qut.edu.au/91754/1/Winsvold2015NeurolGenet.pdf

http://eprints.qut.edu.au/91754/2/Winsvold2015NeurolGenet%5BSuppl%5D.zip

DOI:10.1212/NXG.0000000000000010

Winsvold, B. S., Nelson, C. P., Malik, R., Gormley, P., Anttila, V., Vander Heiden, J., Elliott, K. S., Jacobsen, L. M., Palta, P., Amin, N., de Vries, B., Hamalainen, E., Freilinger, T., Ikram, M. A., Kessler, T., Koiranen, M., Ligthart, L., McMahon, G., Pedersen, L. M., Willenborg, C., Won, H.-H., Olesen, J., Artto, V., Assimes, T. L., Blankenberg, S., Boomsma, D. I., Cherkas, L., Davey Smith, G., Epstein, S. E., Erdmann, J., Ferrari, M. D., Gobel, H., Hall, A. S., Jarvelin, M.-R., Kallela, M., Kaprio, J., Kathiresan, S., Lehtimaki, T., McPherson, R., Marz, W., Nyholt, D.R., O'Donnell, C. J., Quaye, L., Rader, D. J., Raitakari, O., Roberts, R., Schunkert, H., Schurks, M., Stewart, A. F. R., Terwindt, G. M., Thorsteinsdottir, U., van den Maagdenberg, A. M. J. M., van Duijn, C., Wessman, M., Kurth, T., Kubisch, C., Dichgans, M., Chasman, D. I., Cotsapas, C., Zwart, J.-A., Samani, N. J., & Palotie, A. (2015) Genetic analysis for a shared biological basis between migraine and coronary artery disease. Neurology: Genetics, 1(1), e10.

Direitos

Copyright 2015 American Academy of Neurology

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

Fonte

School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation

Tipo

Journal Article