Positive genetic correlations of migraine with diastolic blood pressure (BP) and systolic BP exist, supporting the notions that diastolic BP plays a critical role in migraine susceptibility and BP and migraine share underlying biological mechanisms, according to a study published in Nature Communications.
The link between migraine and the vascular system has been substantiated by numerous studies yielding physiologic and epidemiologic evidence, the authors write, including migraine comorbidities of vascular conditions such as stroke and coronary artery disease.
Genome-wide association studies (GWAS) have also found “approximately 40% of the genome-wide significant GWAS loci for migraine map near genes with known or suspected vascular functions, including vascular development, endothelial structure, and smooth muscle function.”
BP-lowering medications have also been shown to provide prophylactic benefit to many migraineurs. However, associations of BP with migraine are not consistent. To gain insight into mechanistic links between BP and migraine, the researchers leveraged large-scale genetic summary-level data and applied preceding genetic methods.
Using the most recent GWAS summary-level data from the International Headache Genetics Consortium for migraine, the researchers conducted a meta-analysis on 59,674 cases and 316,078 controls from 22 cohort-level GWASs. BP meta-analysis summary statistics combined 757,601 participants from the United Kingdom Biobank (n =?458,577) and International Consortium of Blood Pressure GWASs (n?=?299,024 across 77 cohorts).
Conventional cross-trait linkage disequilibrium score regression (LDSC) and the genetic covariance analyzer were used to evaluate genetic correlation between migraine and BP, while transcriptome-wide association studies (TWAS) were used to identify genes whose expression pattern across tissues implicated etiology or biological mechanisms shared by migraine and BP measures.
Analyses revealed:
- A positive overall genetic correlation of migraine with diastolic BP (rg?=?0.11; Wald test P?=?3.56 × 10?06) and systolic BP (rg?=?0.06; Wald test P?=?.01), but not pulse pressure (rg?=??0.01; Wald test P?=?.75) using LDSC
- Diastolic BP was consistently correlated with both migraine with aura (rg?=?0.17; Wald test P?=?1.50 × 10?03) and migraine without aura (rg?=?0.14; Wald test P?=?1.20 × 10?03), whereas systolic BP was only marginally correlated with migraine with aura (rg?=?0.10; Wald test P?=?.04)
- Partitioned genetic correlation suggested that shared effects were concentrated in some chromosomes, with the strongest positive genetic correlation observed at chromosome 22
