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ABSTRACT Objective The association between eating disorders and migraine remains unclear. Method We identified women with lifetime diagnoses of anorexia nervosa (AN) ( N = 55) and bulimia nervosa (BN) (N = 60) and their co-twins from the FinnTwin16 cohort born in 1975-1979 ( N = 2,825 women). Eating disorder and major depressive disorder (MDD) diagnoses were obtained from clinical interviews and data on migraine by self-report questionnaire. The women with eating disorders were compared with their unaffected co-twins and with unrelated women from the same birth cohorts. Results The prevalence of migraine was 12% in the general female population, but 22% for both AN and BN (odds ratio 2.0, p = .04). The prevalence of MDD was high in women with an eating disorder (42%). MDD was strongly associated with migraine (odds ratio 3.0, p < .0001) and explained the association between eating disorders and migraine. The highest migraine prevalence (36%) was found in women with both an eating disorder and MDD. Pairwise twin analyses also supported the clustering of migraine, MDD and eating disorders. Discussion Women with a lifetime diagnosis of an eating disorder were twice as likely to report a history of migraine as unrelated women from the same cohort; this relationship was explained by comorbid MDD. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:884-887) [ABSTRACT FROM AUTHOR]

Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology. [ABSTRACT FROM AUTHOR]

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]

Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and traitcomponent analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22q23 locus probably contains one or more migraine susceptibility variants. [ABSTRACT FROM AUTHOR]

Migraine is a complex neurovascular disorder with substantial evidence supporting a genetic contribution. Prior attempts to localize susceptibility loci for common forms of migraine have not produced conclusive evidence of linkage or association. To date, no genomewide screen for migraine has been published. We report results from a genomewide screen of 50 multigenerational, clinically well-defined Finnish families showing intergenerational trans-mission of migraine with aura (MA). The families were screened using 350 polymorphic microsatellite markers, with an average intermarker distance of 11 cM. Significant evidence of linkage was found between the MA phenotype and marker D4S1647 on 4q24. Using parametric two-point linkage analysis and assuming a dominant mode of inheritance, we found for this marker a maximum LOD score of 4.20 under locus homogeneity (P = .000006 ) or locus heterogeneity (P = .000011 ). Multipoint parametric (HLOD = 4.45; P= .0000058) and nonparametric (NPL&suball; = 3.43; P = .0007) analyses support linkage in this region. Statistically significant linkage was not in any other chromosomal region. [ABSTRACT FROM AUTHOR]