Association and genetic overlap between clinical chemistry tests and migraine

Cephalalgia. 2021 Oct;41(11-12):1208-1221. doi: 10.1177/03331024211018131. Epub 2021 Jun 15.

Abstract

Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine.

Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals.

Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86-1.21; 1 × 10-4 < p < 3 × 10-2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease.

Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

Keywords: Biochemistry tests; Mendelian randomisation; SNP-based genetic overlap; gene-based genetic overlap; genetic correlation.

MeSH terms

  • Clinical Chemistry Tests
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Humans
  • Iron Deficiencies*
  • Migraine Disorders* / diagnosis
  • Migraine Disorders* / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics