New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis.

Migraine is a common disabling primary headache disorder that is ranked as the most common neurological cause of disability worldwide. Women present with migraine much more frequently than men, but the reasons for this difference are unknown. Migraine heritability is estimated to up to 57%, yet much of the genetic risk remains unaccounted for, especially in non-European ancestry populations. To elucidate the etiology of this common disorder, we conduct a multiethnic genome-wide association meta-analysis of migraine, combining results from the GERA and UK Biobank cohorts, followed by a European-ancestry meta-analysis using public summary statistics. We report 79 loci associated with migraine, of which 45 were novel. Sex-stratified analyses identify three additional novel loci (CPS1, PBRM1, and SLC25A21) specific to women. This large multiethnic migraine study provides important information that may substantially improve our understanding of the etiology of migraine susceptibility.

26,052 European ancestry cases, 487,214 European ancestry controls, 569 East Asian ancestry cases, 6,619 East Asian ancestry controls, 1,142 Hispanic or Latin American cases, 4,695 Hispanic or Latin American controls, 296 African American or Afro-Caribbean cases, 1,747 African American or Afro-Caribbean controls, 208 African ancestry cases, 8,357 African ancestry controls, 278 South Asian ancestry cases, 9,480 South Asian ancestry controls, 307 Other admixed ancestry cases, 7,605 Other admixed ancestry controls