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Meta-Analysis
. 2026 Dec;28(1):107-118.
doi: 10.1080/19585969.2026.2636459. Epub 2026 Mar 9.

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

Chyi-Huey Bai  1   2   3 , Hsien-Yu Fan  4 , Hui-An Lin  2   5   6 , Sheng-Feng Lin  1   2   5   7
Affiliations
Meta-Analysis

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

Chyi-Huey Bai et al. Dialogues Clin Neurosci. 2026 Dec.

Abstract

Background: 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.

Methods: 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).

Results: 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).

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

Keywords: Cognitive impairment; mendelian randomisation; migraine.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flow diagram and design of the study.
See this image and copyright information in PMC

References

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