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Eur J Neurol. 2019 Oct 29. doi: 10.1111/ene.14111. [Epub ahead of print]

Effect of genetic liability to migraine on coronary artery disease and atrial fibrillation: a Mendelian randomization study.

Author information

1
Department of Medicine, Division of Preventive Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
2
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
3
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Abstract

BACKGROUND AND PURPOSE:

Observational studies have implicated migraine as a risk factor for coronary artery disease (CAD) and atrial fibrillation (AF); however, it is unclear whether migraine is causal in this relationship. Potential causality between genetically instrumented liability to migraine and cardiovascular disease outcomes was investigated using two-sample Mendelian randomization.

METHODS:

The exposure comprised 35 independent, genome-wide significant genetic variants identified in the largest published genome-wide association study of migraine (Ncases  = 59 674/Ncontrols = 316 078). The outcome datasets included genome-wide association studies of CAD (76 014/264 785), myocardial infarction (43 676/128 199), angina (10 618/326 065) and AF (60 620/970 216). Mendelian randomization estimates were calculated using inverse-variance weighted regression, and were further assessed with conventional Mendelian randomization sensitivity analyses.

RESULTS:

Evidence was found for a protective effect of migraine liability on CAD (odds ratio 0.86, 95% confidence interval 0.76-0.96, P = 0.003), myocardial infarction (0.86, 0.74-0.96, P = 0.01) and angina (0.86, 0.75-0.99, P = 0.04), but not on AF (1.00, 0.95-1.05, P = 0.88). Analyses by migraine subtype showed an effect of liability to migraine without aura on CAD risk (0.91, 0.84-0.99, P = 0.014), but not of migraine with aura (1.00, 0.97-1.03, P = 0.89). Sensitivity analyses indicated minimal bias by horizontal pleiotropy, outliers, reverse causality or sample overlap.

CONCLUSIONS:

A potentially protective effect of genetically instrumented liability to migraine on CAD risk was identified. Mechanistic research investigating this link is warranted.

KEYWORDS:

Mendelian randomization; coronary artery disease; migraine

PMID:
31661179
DOI:
10.1111/ene.14111

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