Dialogues in clinical neuroscience · 2026
Migraines and the association of cognitive impairment: a one- and two-sample mendelian randomization analysis.
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Bai Chyi-Huey, Fan Hsien-Yu, Lin Hui-An, Lin Sheng-Feng
Аннотация
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.
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.