Migraines and the association of cognitive impairment: a one- and two-sample mendelian randomization analysis

TL;DR

This study uses genetic data to show that migraines are likely to cause cognitive impairment.

Contribution

The study provides causal evidence linking migraines to cognitive impairment using multiple MR strategies.

Findings

A polygenic risk score showed migraines are causally linked to cognitive impairment.

One-sample MR confirmed a causal relationship between migraines and cognitive impairment.

Two-sample MR validated the causal link using independent datasets.

Abstract

Cognitive impairment is widely reported in migraineurs. A Mendelian randomisation (MR) approach, similar to a randomised-controlled trial, employs single-nucleotide polymorphisms (SNPs) to investigate causal relationships.

This study comprised one- and two-sample MR analyses of the Taiwan Biobank. Three strategies were used to obtain causal estimates: (1) a polygenic risk score (PRS) method—several SNPs associated with migraines were constructed as a single instrument variable; (2) a meta-analysis of genome-wide association study (GWAS) statistics for traits of migraines and cognitive impairment in the framework of a one-sample MR; and (3) a two-sample MR analysis with a meta-analysis of GWAS statistics in two distinct datasets (IEU GWAS database and the Taiwan Biobank).

In strategy 1, the PRS constructed by 18 selected SNPs exhibited a causal association with cognitive impairment (β = −2.31, 95% confidence interval [CI]: −4.56 to −0.06). In strategy 2, a one-sample MR showed migraines were causally associated with cognitive impairment (inverse-variance weighted [IVW] estimator β = 2.90; 95% CI: 0.90–4.89). In strategy 3, a two-sample MR validated migraines to be causally associated with cognitive impairment (IVW estimator β = 2.43; 95% CI: 1.08–3.78).

Migraine, a polygenic disorder, is causally associated with cognitive impairment.

Figures