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Genetic analysis for a shared biological basis between migraine and coronary artery disease.pdf (512.83 kB)

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

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posted on 2019-10-02, 15:11 authored by BS Winsvold, CP Nelson, R Malik, P Gormley, V Anttila, J Vander Heiden, KS Elliott, LM Jacobsen, P Palta, N Amin, B de Vries, E Hämäläinen, T Freilinger, MA Ikram, T Kessler, M Koiranen, L Ligthart, G McMahon, LM Pedersen, C Willenborg, H-H Won, J Olesen, V Artto, TL Assimes, S Blankenberg, DI Boomsma, L Cherkas, G Davey Smith, SE Epstein, J Erdmann, MD Ferrari, H Göbel, AS Hall, M-R Jarvelin, M Kallela, J Kaprio, S Kathiresan, T Lehtimäki, R McPherson, W März, DR Nyholt, CJ O'Donnell, L Quaye, DJ Rader, O Raitakari, R Roberts, H Schunkert, M Schürks, AFR Stewart, GM Terwindt, U Thorsteinsdottir, AMJM van den Maagdenberg, C van Duijn, M Wessman, T Kurth, C Kubisch, M Dichgans, DI Chasman, C Cotsapas, J-A Zwart, NJ Samani, A Palotie, CARDIoGRAM Consortium and the International Headache Genetics Consortium
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.

Funding

This work was supported by Academy of Finland (grant 251704 to A.P.), Sigrid Juselius Foundation (to A.P.), SynSys (to A.P.), the Wellcome Trust (grant 098051 to A.P.), EU FP7-242167 (to A.P.), NIH/RFA-HL-12-007, Genomic and Metabolomic Profiling of Finnish Familial Dyslipidemia Families (to A.P.), the South-Eastern Norway Regional Health Authority (grants 2010075 and 2011083 to B.S.W., L.M.J., and J.-A.Z.), the Research Council of Norway (grant 231187/F20 to B.S.W.), and the NIHR Leicester Cardiovascular Biomedical Research Unit and BHF (to C.P.N.). N.J.S. holds a Chair funded by the British Heart Foundation and is an NIHR Senior Investigator. Funding for study cohorts and remaining authors are listed in the acknowledgment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

History

Citation

Neurology Genetics, 2015;1:e10

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Neurology Genetics

Publisher

Lippincott, Williams & Wilkins

issn

2376-7839

Acceptance date

2015-05-27

Copyright date

2015

Available date

2019-10-02

Publisher version

https://ng.neurology.org/content/1/1/e10

Notes

Supplemental data at https://ng.neurology.org/lookup/doi/10.1212/NXG.0000000000000010

Language

en

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