A GENOME-WIDE association study (GWAS) presented at the 2025 American Academy of Neurology (AAN) Annual Meeting in San Diego has identified 778 previously unknown genetic variants associated with migraine, shedding new light on the condition’s genetic underpinnings across racial and ethnic groups.
The study, titled “Multi-ancestry Genome-wide Analysis of 90,600 Migraine Cases in US Veterans,” is part of the Million Veteran Program (MVP), a large-scale, ongoing national biorepository launched in 2011 to examine how genetics, lifestyle, and military exposures contribute to disease risk. This analysis included data from 648,172 U.S. veterans, making it one of the largest and most diverse studies of migraine genetics to date.
Researchers identified 90,600 veterans with a migraine diagnosis based on electronic health records and questionnaires. Migraine prevalence varied across ancestry groups: 13.1% among European ancestry (n=60,957), 16.0% African American (n=19,709), 16.6% Hispanic (n=8,667), and 15.2% Asian (n=1,267).
The GWAS identified 624 significant single nucleotide polymorphisms (SNPs) in the European group, 3 in African Americans, 8 in Hispanics, and 59 in Asians. A pan-ancestry meta-analysis revealed 789 total SNPs associated with migraine, 778 of which were novel findings (p-value < 5E-8). Pathway enrichment analysis indicated involvement of several biological pathways, including interleukin signaling, ionotropic glutamate receptor activity, synaptic vesicle trafficking, and JAK/STAT, EGFR, and PDGF signaling. The identified genetic risk variants showed expression enrichment in neurons, immune cells, microglia, astrocytes, and fibroblasts, suggesting a multi-cellular influence on migraine pathophysiology. These findings not only expand the understanding of migraine genetics but also highlight the importance of diverse population participation in neurologic research. Reference: Xiao M et al. Multi-ancestry Genome-wide Analysis of 90,600 Migraine Cases in US Veterans. 2025 American Academy of Neurology (AAN) Annual Meeting, April 5-9, 2025, San Diego, California, USA.
