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


ABSTRACT: 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.

SUBMITTER: Winsvold BS 

PROVIDER: S-EPMC4821079 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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

Winsvold Bendik S BS   Nelson Christopher P CP   Malik Rainer R   Gormley Padhraig P   Anttila Verneri V   Vander Heiden Jason J   Elliott Katherine S KS   Jacobsen Line M LM   Palta Priit P   Amin Najaf N   de Vries Boukje B   Hämäläinen Eija E   Freilinger Tobias T   Ikram M Arfan MA   Kessler Thorsten T   Koiranen Markku M   Ligthart Lannie L   McMahon George G   Pedersen Linda M LM   Willenborg Christina C   Won Hong-Hee HH   Olesen Jes J   Artto Ville V   Assimes Themistocles L TL   Blankenberg Stefan S   Boomsma Dorret I DI   Cherkas Lynn L   Davey Smith George G   Epstein Stephen E SE   Erdmann Jeanette J   Ferrari Michel D MD   Göbel Hartmut H   Hall Alistair S AS   Jarvelin Marjo-Riitta MR   Kallela Mikko M   Kaprio Jaakko J   Kathiresan Sekar S   Lehtimäki Terho T   McPherson Ruth R   März Winfried W   Nyholt Dale R DR   O'Donnell Christopher J CJ   Quaye Lydia L   Rader Daniel J DJ   Raitakari Olli O   Roberts Robert R   Schunkert Heribert H   Schürks Markus M   Stewart Alexandre F R AF   Terwindt Gisela M GM   Thorsteinsdottir Unnur U   van den Maagdenberg Arn M J M AM   van Duijn Cornelia C   Wessman Maija M   Kurth Tobias T   Kubisch Christian C   Dichgans Martin M   Chasman Daniel I DI   Cotsapas Chris C   Zwart John-Anker JA   Samani Nilesh J NJ   Palotie Aarno A  

Neurology. Genetics 20150601 1


<h4>Objective</h4>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).<h4>Methods</h4>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 assess  ...[more]

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