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Free keywords:
Migraine, subgroups, genome-wide, association, genetic, heterogeneity
Abstract:
Background There has been intensive debate whether migraine with aura
(MA) and migraine without aura (MO) should be considered distinct
subtypes or part of the same disease spectrum. There is also discussion
to what extent migraine cases collected in specialised headache clinics
differ from cases from population cohorts, and how female cases differ
from male cases with respect to their migraine. To assess the genetic
overlap between these migraine subgroups, we examined genome-wide
association (GWA) results from analysis of 23,285 migraine cases and
95,425 population-matched controls.
Methods Detailed heterogeneity analysis of single-nucleotide
polymorphism (SNP) effects (odds ratios) between migraine subgroups was
performed for the 12 independent SNP loci significantly associated
(p<5x10(-8); thus surpassing the threshold for genome-wide significance)
with migraine susceptibility. Overall genetic overlap was assessed using
SNP effect concordance analysis (SECA) at over 23,000 independent SNPs.
Results Significant heterogeneity of SNP effects (p(het)<1.4x10(-3)) was
observed between the MA and MO subgroups (for SNP rs9349379), and
between the clinic- and population-based subgroups (for SNPs rs10915437,
rs6790925 and rs6478241). However, for all 12 SNPs the risk-increasing
allele was the same, and SECA found the majority of genome-wide SNP
effects to be in the same direction across the subgroups.
Conclusions Any differences in common genetic risk across these
subgroups are outweighed by the similarities. Meta-analysis of
additional migraine GWA datasets, regardless of their major subgroup
composition, will identify new susceptibility loci for migraine.
