Association Between Genetic Variants and Clinical Features Among Sub-Classes of Migraine and Probable Migraine

Abstract

Migraine is a prevalent and disabling neurological disease, characterized by substantial clinical heterogeneity. The current study examined 46 single nucleotide polymorphisms (SNPs) recently identified in a meta-analysis of genome-wide association studies for association with migraine. Using a likelihood framework approach and application of latent class methodology, we explore the selective association of these SNPs with individual symptoms and possible substructures in the Women’s Genome Health Study, a large population-based cohort of women, including 3,003 active migraineurs and 18,108 controls without migraine. We identified 15 SNPs indicating 12 loci with significant preferential associations with migraine features, six of which were previously unreported. Our findings reflect the multifactorial pathophysiology underlying migraine and highlight the importance of assessing and understanding the selective genetic association with the individual features, as they may indicate diverse yet related biological pathways that are not induced by diagnostic criteria. This deeper and differentiated understanding of migraine can form the foundation for a personalized therapeutic approach with much greater precision.