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Abstract Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30–1.84, P = 6.87 × 10−7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

Psychiatric disorders are often accompanied by alterations in BMI and body composition due to changes in eating behaviour and physical activity. Here, Hübel et al. study the genetic overlap between these traits and find that genetic correlations between psychiatric disorders and body composition are sex-specific and evident only in adulthood.

Understanding of the causes and treatment of migraine is incomplete. Here, the authors detect pleiotropic genetic effects and causal relationships between migraine and 58 proteins that are largely distinct from migraine-associated loci identified by GWAS.

The association between blood pressure (BP) and migraine is poorly understood. Here, the authors explore this relationship using summary-level GWAS data for BP and migraine. Cross-trait meta-analysis reveals shared loci between BP and migraine, while Mendelian randomization suggests that diastolic BP specifically plays a key role in migraine susceptibility.