Integrating Genome-Wide Association and Blood Genomic Profiling Data to Characterise Migraine Risk Loci

Abstract

Migraine is a frequent, debilitating and painful headache disorder that normally affects people during their most productive years of life (25% of females and 8% of males).Genome-wide association studies have identified 44 independent single nucleotide polymorphisms associated with migraine, however the causal genes and pathogenic mechanisms underlying the disorder remain unknown. Therefore, we performed a multi-staged integrated study of gene expression and DNA methylation in a large sample of migraine cases and non-migraine controls from the Brisbane Systems Genetics Study. We identified several gene expression networks and differentially methylated regions associated with migraine, which were subsequently characterised using robust statistical and pathway-based approaches. Integration of existing genomewide association data with gene expression and methylation data prioritised migraine susceptibility genes for further functional characterisation. This study suggests the use of multiple molecular data to study existing migraine loci has the potential to provide a substantial contribution to understanding the underlying genetic architecture and biological mechanisms of migraine, and may help in the development of diagnostic tests and new targets for drug therapy.3