Objective: To investigate potential causality between genetic liability to migraine and Alzheimer's disease, intelligence, and brain volume using two-sample Mendelian randomization.
Methods: The exposure consisted of independent genetic variants associated with migraine in the largest (59,674 cases/316,078 controls) published genome-wide association study. Outcomes included Alzheimer's disease (71,880 cases/383,378 controls), a measure of general intelligence (n = 269,867), intracranial volume (n = 11,373), and seven subcortical brain volumes (n ∼ 13,000), all with available genome-wide association study summary statistics. Mendelian randomization effects were estimated using inverse-variance weighted analysis.
Results: Genetic liability to migraine did not associate with Alzheimer's disease (odds ratio [95% confidence interval] 1.01 [1.00-1.02], p = 0.07), intelligence (standardized beta [95% confidence interval] 0.01 [0.00-0.02], p = 0.13), or any brain volume measures (all p > 0.05). No individual migraine variant associated with any of the outcomes at genome-wide significance.
Conclusions: These data do not support a causal effect of migraine liability on Alzheimer's disease, intelligence, or brain volume.
Keywords: Mendelian randomization; Migraine; brain volume; cognition.