# 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.

## Key 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.