No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study.

Objective: To determine the association between human leukocyte antigen (HLA) alleles and migraine, migraine subtypes, and sex-specific factors.

Background: It has long been hypothesized that inflammation contributes to migraine pathophysiology. This study examined the association between migraine and alleles in the HLA system, a key player in immune response and genetic diversity.

Metabolic Dysfunction in New-Onset Idiopathic Intracranial Hypertension: Identification of Novel Biomarkers.

Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity.

Genome-wide association study reveals a locus in ADARB2 for complete freedom from headache in Danish Blood Donors.

Headache disorders are the most common disorders of the nervous system. The lifetime prevalence of headache disorders show that some individuals never experience headache. The etiology of complete freedom from headache is not known.

Reduced plasma calcitonin gene-related peptide level identified in cluster headache: A prospective and controlled study.

Background: The role of calcitonin gene-related peptide (CGRP) in the cyclic pattern of cluster headache is unclear. To acquire biological insight and to comprehend why only episodic cluster headache responds to CGRP monoclonal antibodies, we examined whether plasma CGRP changes between disease states (i.e.

Blood donation and migraine relief: A national population cohort study in Denmark.

Introduction: Migraine is a prevalent neurological headache disorder. Due to challenges associated with finding effective treatment, many individuals with migraine feel compelled to explore alternative treatment strategies, such as blood donation, hypothesized to provide migraine relief.

Methods: Through logistic, Poisson, and Cox regression methods, we examined the links between migraine and blood donation activities in two population cohorts: Danish blood donors in the Scandinavian Donations and Transfusions Database (SCANDAT-DK, N >1 million) and the Danish Blood Donor Study (N ~ 100,000).

Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms.

Migraine is a common, polygenic disorder that is characterized by moderate to severe headache attacks. Migraine attacks are commonly treated with triptans, i.e.

DanMAC5: a browser of aggregated sequence variants from 8,671 whole genome sequenced Danish individuals.

Objectives: Allele counts of sequence variants obtained by whole genome sequencing (WGS) often play a central role in interpreting the results of genetic and genomic research. However, such variant counts are not readily available for individuals in the Danish population. Here, we present a dataset with allele counts for sequence variants (single nucleotide variants (SNVs) and indels) identified from WGS of 8,671 (5,418 females) individuals from the Danish population.

Population-Based Characterization of Menstrual Migraine and Proposed Diagnostic Criteria.

Importance: There is a need for better recognition and more extensive research into menstrual migraine (MM) in the general population, and a revision of the diagnostic criteria for MM is warranted to move the field forward. Increased understanding of MM is crucial for improving clinical care, diagnosis, and therapy for MM.

Objectives: To assess the clinical characteristics of MM, including severity and treatment response, and to propose new diagnostic criteria for pure MM and menstrually related migraine.

Sex differences in clinical characteristics of migraine and its burden: a population-based study.

Background And Purpose: Understanding migraine in a sex-specific manner is crucial for improving clinical care, diagnosis and therapy for both females and males. Here, data on sex differences are provided in the presentation of migraine in a large European-based population cohort, which is representative of the general population.

Methods: A population-based study of 62,672 Danish blood donors (both present and previous donors), of whom 12,658 had migraine, was performed.

Multi-omics to predict changes during cold pressor test.

Background: The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. We hypothesize, that performing multi-omic analyses during CPT gives the opportunity to home in on molecular mechanisms involved. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken.

Population-based prevalence of cranial autonomic symptoms in migraine and proposed diagnostic appendix criteria.

Background: Migraine with cranial autonomic symptoms is well described in the literature, but its prevalence in previous studies varies enormously. A precise estimate of the prevalence in a population-based material is important because migraine with cranial autonomic symptoms might represent an endophenotype, in which genetic and pathophysiological features differ from those without cranial autonomic features. The aim of the present study, therefore, was to estimate the prevalence in a big population-based sample using both questionnaire-based diagnosis (N = 12,620) and interview-based diagnosis (N = 302).

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura.

Smooth muscle ATP-sensitive potassium channels mediate migraine-relevant hypersensitivity in mouse models.

Background: Opening of K channels by systemic levcromakalim treatment triggers attacks in migraine patients and hypersensitivity to von Frey stimulation in a mouse model. Blocking of these channels is effective in several preclinical migraine models. It is unknown in what tissue and cell type K-induced migraine attacks are initiated and which K channel subtype is targeted.

Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache.

Objective: Identifying common genetic variants that confer genetic risk for cluster headache.

Methods: We conducted a case-control study in the Dutch Leiden University Cluster headache neuro-Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord-Trøndelag Health Survey (HUNT).

Changes in the gene expression profile during spontaneous migraine attacks.

Migraine attacks are delimited, allowing investigation of changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore, we hypothesized that changes in RNA expression during and outside a spontaneous migraine attack exist which are specific to migraine. Twenty-seven migraine patients were assessed during a spontaneous migraine attack, including headache characteristics and treatment effect.

Twenty-five years of triptans - a nationwide population study.

Background: The efficacy of triptans as the main acute treatment strategy for migraine headache at the population-wide level needs to be understood to inform clinical decision-making. We summarise key trends in triptan use using more than 25 years of Danish nationwide data.

Methods: We conducted a nationwide register-based cohort study based on all Danish residents with access to public healthcare between 1 January 1994 and 31 October 2019 and summarise informative trends of all purchases of triptans in Denmark in the same period.

Chronic migraine: Genetics or environment?

Background: The transition from episodic migraine to chronic migraine, migraine chronification, is usually a gradual process, which involves multiple risk factors. To date, studies of the genetic risk factors for chronic migraine have focused primarily on candidate-gene approaches using healthy individuals as controls.

Aims And Methods: In this study, we used a large cohort of migraine families and unrelated migraine patients (n > 2200) with supporting genotype and whole-genome sequencing data.

Functional gene networks reveal distinct mechanisms segregating in migraine families.

Migraine is the most common neurological disorder worldwide and it has been shown to have complex polygenic origins with a heritability of estimated 40-70%. Both common and rare genetic variants are believed to underlie the pathophysiology of the prevalent types of migraine, migraine with typical aura and migraine without aura. However, only common variants have been identified so far.

Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease.

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons.

Prevalence and socio-demographic characteristics of persons who have never had a headache among healthy voluntary blood donors - a population-based study.

Introduction: Headache is an extremely prevalent disorder with a lifetime prevalence of 90-99%. However, a small fraction of people never experiences a headache. Research on people without headache could uncover protective factors in headache, but to our knowledge no study on headache-free individuals has been published.

Familial analysis reveals rare risk variants for migraine in regulatory regions.

The most recent genome-wide association study of migraine increased the total number of known migraine risk loci to 38. Still, most of the heritability of migraine remains unexplained, and it has been suggested that rare gene dysregulatory variants play an important role in migraine etiology. Addressing the missing heritability of migraine, we aim to fine-map signals from the known migraine risk loci to regulatory mechanisms and associate these to downstream genic targets.

Migraine polygenic risk score associates with efficacy of migraine-specific drugs.

Objective: To assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response.

Methods: We interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped.