Migraine genetics: Status and road forward

Cephalalgia, vol. 43, pp. 3331024221145962

Abstract

BACKGROUND: Migraine is considered a multifactorial genetic disorder. Different platforms and methods are used to unravel the genetic basis of migraine. Initially, linkage analysis in multigenerational families followed by Sanger sequencing of protein-coding parts (exons) of genes in the genomic region shared by affected family members identified high-effect risk DNA mutations for rare Mendelian forms of migraine, foremost hemiplegic migraine. More recently, genome-wide association studies testing millions of DNA variants in large groups of patients and controls have proven successful in identifying many dozens of low-effect risk DNA variants for the more common forms of migraine with the number of associated DNA variants increasing steadily with larger sample sizes. Currently, next-generation sequencing, utilising whole exome and whole genome sequence data, and other omics data are being used to facilitate their functional interpretation and the discovery of additional risk factors. Various methods and analysis tools, such as genetic correlation and causality analysis, are used to further characterise genetic risk factors. FINDINGS: < 0.1) genome-wide significant single nucleotide polymorphisms (SNPs), of which 99 were unique to Hautakangas et al., 11 were unique to Choquet et al., and 68 were identified by both studies. When considering that Choquet et al. also identified three SNPs in a female-specific genome-wide association studies then these two recent studies identified 181 independent SNPs robustly associated with migraine. Cross-trait and causal analyses are beginning to identify and characterise specific biological factors that contribute to migraine risk and its comorbid conditions. CONCLUSION: This review provides a timely update and overview of recent genetic findings in migraine.

Authors 4

1. Aster V. E. Harder Aachen Department of Human Genetics Department of Neurology, Leiden University Medical Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

2. Gisela Marie Terwindt Aachen Department of Human Genetics

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands

3. Dale R. Nyholt

   Queensland University of Technology

   Affiliation as printed

   School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Australia

4. Arn M. J. M. van den Maagdenberg corresponding Aachen Department of Human Genetics Department of Neurology, Leiden University Medical Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands