학술논문
Concordance of genetic risk across migraine subgroups: Impact on current and future genetic association studies.
Document Type
Article
Author
Nyholt, Dale R; Anttila, Verneri; Winsvold, Bendik S; Kurth, Tobias; Stefansson, Hreinn; Kallela, Mikko; Malik, Rainer; Vries, Boukje de; Terwindt, Gisela M; Ikram, M Arfan; Stam, Anine H; Ligthart, Lannie; Freilinger, Tobias; Alexander, Michael; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Aromaa, Arpo; Eriksson, Johan G; Kaprio, Jaakko
Source
Subject
*MIGRAINE
*GENOMICS
*GENETIC research
*HETEROGENEITY
*HEADACHE
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Language
ISSN
0333-1024
Abstract
Background: There has been intensive debate whether migraine with aura (MA) and migraine without aura (MO) shouldbe considered distinct subtypes or part of the same disease spectrum. There is also discussion to what extent migrainecases collected in specialised headache clinics differ from cases from population cohorts, and how female cases differfrom male cases with respect to their migraine. To assess the genetic overlap between these migraine subgroups, weexamined genome-wide association (GWA) results from analysis of 23,285 migraine cases and 95,425 populationmatchedcontrols.Methods: Detailed heterogeneity analysis of single-nucleotide polymorphism (SNP) effects (odds ratios) between migrainesubgroups was performed for the 12 independent SNP loci significantly associated (p<5x10-8; thus surpassing thethreshold for genome-wide significance) with migraine susceptibility. Overall genetic overlap was assessed using SNPeffect concordance analysis (SECA) at over 23,000 independent SNPs.Results: Significant heterogeneity of SNP effects (phet<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 andrs6478241). However, for all 12 SNPs the risk-increasing allele was the same, and SECA found the majority of genomewideSNP 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. Metaanalysisof additional migraine GWA datasets, regardless of their major subgroup composition, will identify new susceptibilityloci for migraine. [ABSTRACT FROM AUTHOR]