Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Migraine Disorders: HELP
Articles from Brisbane
Based on 82 articles published since 2008
||||

These are the 82 published articles about Migraine Disorders that originated from Brisbane during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Review Novel hypotheses emerging from GWAS in migraine? 2019

van den Maagdenberg, Arn M J M / Nyholt, Dale R / Anttila, Verneri. ·Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands. a.m.j.m.van_den_Maagdenberg@lumc.nl. · Department of Neurology, Leiden University Medical Centre, 9600, 2300 RC, Leiden, The Netherlands. a.m.j.m.van_den_Maagdenberg@lumc.nl. · School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia. · Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. · Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. · Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ·J Headache Pain · Pubmed #30634909.

ABSTRACT: Recent technical advances in genetics made large-scale genome-wide association studies (GWAS) in migraine feasible and have identified over 40 common DNA sequence variants that affect risk for migraine types. Most of the variants, which are all single nucleotide polymorphisms (SNPs), show robust association with migraine as evidenced by the fact that the vast majority replicate in subsequent independent studies. However, despite thorough bioinformatic efforts aimed at linking the migraine risk SNPs with genes and their molecular pathways, there remains quite some discussion as to how successful this endeavour has been, and their current practical use for the diagnosis and treatment of migraine patients. Although existing genetic information seems to favour involvement of vascular mechanisms, but also neuronal and other mechanisms such as metal ion homeostasis and neuronal migration, the complexity of the underlying genetic pathophysiology presents challenges to advancing genetic knowledge to clinical use. A major issue is to what extent one can rely on bioinformatics to pinpoint the actual disease genes, and from this the linked pathways. In this Commentary, we will provide an overview of findings from GWAS in migraine, current hypotheses of the disease pathways that emerged from these findings, and some of the major drawbacks of the approaches used to identify the genes and pathways. We argue that more functional research is urgently needed to turn the hypotheses that emerge from GWAS in migraine to clinically useful information.

2 Review Ion channelopathies and migraine pathogenesis. 2017

Albury, Cassie L / Stuart, Shani / Haupt, Larisa M / Griffiths, Lyn R. ·Genomics Research Centre, Institute for Biomedical Health and Innovation, Queensland University of Technology, Brisbane, QLD, 4059, Australia. · Genomics Research Centre, Institute for Biomedical Health and Innovation, Queensland University of Technology, Brisbane, QLD, 4059, Australia. lyn.griffiths@qut.edu.au. ·Mol Genet Genomics · Pubmed #28389699.

ABSTRACT: Migraine is a common neurological disorder that affects approximately 12-20% of the general adult population. Migraine pathogenesis is complex and not wholly understood. Molecular genetic investigations, imaging and biochemical studies, have unveiled a number of interconnected neurological pathways which seem to have a cause and effect component integral to its cause. Much weight of migraine attack initiation can be placed on the initial trigger and the pathways involved in its neuronal counter reaction. Ion channels play a large role in the generation, portrayal and mitigation of the brains response to external triggers. Several genetic studies have identified and implicated a number of ion channelopathy genes which may contribute to this generalised process. This review will focus on the genetics of migraine with particular emphasis placed on the potentially important role genes HEPH (responsible for iron transport and homeostasis) and KCNK18 (important for the transport and homeostasis of potassium) play in migraine cause.

3 Review Genetic and biochemical changes of the serotonergic system in migraine pathobiology. 2017

Gasparini, Claudia Francesca / Smith, Robert Anthony / Griffiths, Lyn Robyn. ·Menzies Health Institute Queensland, Griffith University Gold Coast, Parklands Drive, Southport, QLD, 4222, Australia. · Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Musk Ave, Kelvin Grove, QLD, 4059, Australia. · Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Musk Ave, Kelvin Grove, QLD, 4059, Australia. lyn.griffiths@qut.edu.au. ·J Headache Pain · Pubmed #28194570.

ABSTRACT: Migraine is a brain disorder characterized by a piercing headache which affects one side of the head, located mainly at the temples and in the area around the eye. Migraine imparts substantial suffering to the family in addition to the sufferer, particularly as it affects three times more women than men and is most prevalent between the ages of 25 and 45, the years of child rearing. Migraine typically occurs in individuals with a genetic predisposition and is aggravated by specific environmental triggers. Attempts to study the biochemistry of migraine began as early as the 1960s and were primarily directed at serotonin metabolism after an increase of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin was observed in urine of migraineurs. Genetic and biochemical studies have primarily focused on the neurotransmitter serotonin, considering receptor binding, transport and synthesis of serotonin and have investigated serotonergic mediators including enzymes, receptors as well as intermediary metabolites. These studies have been mainly assayed in blood, CSF and urine as the most accessible fluids. More recently PET imaging technology integrated with a metabolomics and a systems biology platform are being applied to study serotonergic biology. The general trend observed is that migraine patients have alterations of neurotransmitter metabolism detected in biological fluids with different biochemistry from controls, however the interpretation of the biological significance of these peripheral changes is unresolved. In this review we present the biology of the serotonergic system and metabolic routes for serotonin and discuss results of biochemical studies with regard to alterations in serotonin in brain, cerebrospinal fluid, saliva, platelets, plasma and urine of migraine patients.

4 Review Genetic insights into migraine and glutamate: a protagonist driving the headache. 2016

Gasparini, Claudia F / Smith, Robert A / Griffiths, Lyn R. ·Menzies Health Institute Queensland, Griffith University Gold Coast, Parklands Drive, Southport, QLD 4222, Australia. · Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Musk Ave, Kelvin Grove, QLD 4059, Australia. · Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Musk Ave, Kelvin Grove, QLD 4059, Australia. Electronic address: lyn.griffiths@qut.edu.au. ·J Neurol Sci · Pubmed #27423601.

ABSTRACT: Migraine is a complex polygenic disorder that continues to be a great source of morbidity in the developed world with a prevalence of 12% in the Caucasian population. Genetic and pharmacological studies have implicated the glutamate pathway in migraine pathophysiology. Glutamate profoundly impacts brain circuits that regulate core symptom domains in a range of neuropsychiatric conditions and thus remains a "hot" target for drug discovery. Glutamate has been implicated in cortical spreading depression (CSD), the phenomenon responsible for migraine with aura and in animal models carrying FHM mutations. Genotyping case-control studies have shown an association between glutamate receptor genes, namely, GRIA1 and GRIA3 with migraine with indirect supporting evidence from GWAS. New evidence localizes PRRT2 at glutamatergic synapses and shows it affects glutamate signalling and glutamate receptor activity via interactions with GRIA1. Glutamate-system defects have also been recently implicated in a novel FHM2 ATP1A2 disease-mutation mouse model. Adding to the growing evidence neurophysiological findings support a role for glutamate in cortical excitability. In addition to the existence of multiple genes to choreograph the functions of fast-signalling glutamatergic neurons, glutamate receptor diversity and regulation is further increased by the post-translational mechanisms of RNA editing and miRNAs. Ongoing genetic studies, GWAS and meta-analysis implicate neurogenic mechanisms in migraine pathology and the first genome-wide associated locus for migraine on chromosome X. Finally, in addition to glutamate modulating therapies, the kynurenine pathway has emerged as a candidate for involvement in migraine pathophysiology. In this review we discuss recent genetic evidence and glutamate modulating therapies that bear on the hypothesis that a glutamatergic mechanism may be involved in migraine susceptibility.

5 Review Genome-wide association studies in migraine: current state and route to follow. 2016

Nyholt, Dale R / van den Maagdenberg, Arn M J M. ·aStatistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia bDepartments of Human Genetics and Neurology, Leiden University Medical Center, Leiden, The Netherlands. ·Curr Opin Neurol · Pubmed #26967494.

ABSTRACT: PURPOSE OF REVIEW: Genome-wide association studies (GWAS) have revealed over a dozen genetic factors robustly associated with the common forms of migraine. The identification of these factors, the implicated biological mechanisms, and whether they are of use in basic research and clinic practice will be discussed. RECENT FINDINGS: Several GWAS have been performed in recent years. New approaches are being tested to identify how information of genetic susceptibility factors can be used in research and the clinic. Still, we are only at the beginning of understanding how the genetic factors may be involved in migraine pathophysiology. SUMMARY: The identification of genetic factors that confer risk for the common forms of migraine by GWAS has given insight into the genetic underpinning of migraine pathophysiology. Still, the interpretation of the findings of GWAS is not straightforward. Various strategies are being tested to investigate which pathophysiological mechanisms are involved, how they can be studied, and what this means for clinical diagnosis, and even care.

6 Review Genetic epidemiology of migraine and depression. 2016

Yang, Yuanhao / Ligthart, Lannie / Terwindt, Gisela M / Boomsma, Dorret I / Rodriguez-Acevedo, Astrid J / Nyholt, Dale R. ·Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia. · Department of Biological Psychology, VU University, The Netherlands EMGO+ Institute for Health and Care Research, VU University Medical Centre, The Netherlands. · Department of Neurology, Leiden University Medical Centre, The Netherlands. · Department of Biological Psychology, VU University, The Netherlands. · Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia d.nyholt@qut.edu.au. ·Cephalalgia · Pubmed #26966318.

ABSTRACT: BACKGROUND: Migraine and major depressive disorder (commonly referred to as depression) are both common disorders with a significant impact on society. Studies in both clinical and community-based settings have demonstrated a strong relationship between migraine and depression. In addition to complicating the diagnosis, depression that is comorbid with migraine may lower treatment adherence, increase risk of medication overuse and is associated with migraine chronification, thus leading to higher direct and indirect costs and poorer health-related outcomes with increased disability. AIM: The aim of this review is to summarise the current knowledge on the genetic epidemiology of migraine and depression and the possible biological mechanisms underlying their comorbidity. METHODS: We present a narrative review reporting on the current literature. RESULTS AND CONCLUSIONS: Epidemiological findings indicate that there is a bidirectional relationship between migraine and depression, with one disorder increasing the risk for the other and vice versa, suggesting shared biological mechanisms. Twin and family studies indicate that this bidirectional relationship can be explained, at least partly, by shared underlying genetically determined disease mechanisms. Although no genes have been robustly associated with the aetiology of both migraine and depression, genes from serotonergic, dopaminergic and GABAergic systems together with variants in the MTHFR and BDNF genes remain strong candidates.

7 Review Blood gene expression studies in migraine: Potential and caveats. 2016

Gerring, Zachary / Rodriguez-Acevedo, Astrid J / Powell, Joseph E / Griffiths, Lyn R / Montgomery, Grant W / Nyholt, Dale R. ·Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. · Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia The Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. · Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. · Molecular Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia d.nyholt@qut.edu.au. ·Cephalalgia · Pubmed #26862113.

ABSTRACT: BACKGROUND: Global gene expression analysis may be used to obtain insights into the functional processes underlying migraine. However, there is a shortage of high-quality post-mortem brain tissue samples for genetic analysis. One approach is to use a more accessible tissue as a surrogate, such as peripheral blood. PURPOSE: Discuss the benefits and caveats of blood genomic profiling in migraine and its potential application in the development of biomarkers of migraine susceptibility and outcome. Demonstrate the utility of blood-based expression profiles in migraine by analysing pilot Illumina HT-12 expression data from 76 (38 case, 38 control) whole-blood samples. CONCLUSION: Current evidence suggests peripheral blood is a biologically valid substrate for genetic studies of migraine, and may be used to identify biomarkers and therapeutic pathways. Pilot blood gene expression data confirm that expression profiles significantly differ between migraine case and non-migraine control individuals.

8 Review Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility. 2014

Roos-Araujo, Deidré / Stuart, Shani / Lea, Rod A / Haupt, Larisa M / Griffiths, Lyn R. ·Genomics Research Centre, Institute for Biomedical Health and Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia. · Genomics Research Centre, Institute for Biomedical Health and Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia. Electronic address: lyn.griffiths@qut.edu.au. ·Gene · Pubmed #24704026.

ABSTRACT: Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.

9 Review Management of chronic headache. 2014

Beran, Roy G. ·MBBS, MD, FRCP, FRACGP, FACLM, B LegS, Consultant Neurologist; Conjoint Associate Professor of Medicine, University of New South Wales; Professor, School of Medicine, Griffith University; ·Aust Fam Physician · Pubmed #24600670.

ABSTRACT: BACKGROUND: Headache remains the most common cause of neurological consultation in clinical practice for which correct diagnosis and treatment are essential. OBJECTIVE: This article provides a review of headache presentation and management, with an emphasis on chronic headaches and the differentiation between migraine and tension-type headache (TTH). DISCUSSION: By far the most important diagnostic tool for proper headache diagnosis is the taking of a concise and representative history of the headaches. Migraine and TTH exist along a continuum and identification of the patient's position on this continuum has important implications for management.

10 Review A possible role for mitochondrial dysfunction in migraine. 2012

Stuart, S / Griffiths, L R. ·Genomics Research Centre, Griffith Health Institute, Griffith University, Gold Coast Campus, Gold Coast, QLD 4222, Australia. ·Mol Genet Genomics · Pubmed #23052833.

ABSTRACT: Migraine is a common neurological disorder characterised by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia and occasionally visual sensory disturbances. Migraine is a complex disease caused by an interplay between predisposing genetic variants and environmental factors. It affects approximately 12 % of studied Caucasian populations with affected individuals being predominantly female. Genes involved in neurological, vascular or hormonal pathways have all been implicated in predisposition towards developing migraine. All of these are nuclear encoded genes, but given the role of mitochondria in a number of neurological disorders and in energy production it is possible that mitochondrial variants may play a role in the pathogenesis of this disease. Mitochondrial DNA has been a useful tool for studying population genetics and human genetic diseases due to the clear inheritance shown through successive generations. Given the clear gender bias found in migraine patients it may be important to investigate X-linked inheritance and mitochondrial-related variants in this disorder. This paper explores the possibility that mitochondrial DNA changes may play a role in migraine. Few variants in the mitochondrial genome have so far been investigated in migraine and new studies should be aimed towards investigating the role of mitochondrial DNA in this common disorder.

11 Review The role of the MTHFR gene in migraine. 2012

Stuart, Shani / Cox, Hannah C / Lea, Rod A / Griffiths, Lyn R. ·Genomics Research Centre, Griffith Health Institute, Griffith University, Gold Coast Campus, Southport, QLD, Australia. ·Headache · Pubmed #22375693.

ABSTRACT: Migraine is a common neurological disorder and is characterized by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia, and occasionally, visual sensory disturbances. A number of genes have been implicated in the pathogenesis of this disease, including genes involved in regulating the vascular system. Of particular importance are the methylenetetrahydrofolate reductase (MTHFR) gene and the role it plays in migraine with aura. Migraine with aura has previously been shown to have a significant comorbidity with stroke, making the vascular class of genes a priority for migraine studies. In this report, we outline the importance of the MTHFR gene in migraine and also discuss the use of a genetic isolate to investigate MTHFR genetic variants. From this study, 3 MTHFR single nucleotide polymorphisms showing association with migraine in the Norfolk Island population have been identified, thus reinforcing the potential role of MTHFR in migraine susceptibility. Further studies will continue to build a gene profile of variants involved in the complex disease migraine and improve understanding of the underlying genetic causes of this disorder.

12 Review Identification of molecular genetic factors that influence migraine. 2011

Maher, Bridget H / Griffiths, Lyn R. ·Genomics Research Centre, School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast campus, Gold Coast, QLD, 4222, Australia. ·Mol Genet Genomics · Pubmed #21519858.

ABSTRACT: Migraine is a common neurological disorder with a strong genetic basis. However, the complex nature of the disorder has meant that few genes or susceptibility loci have been identified and replicated consistently to confirm their involvement in migraine. Approaches to genetic studies of the disorder have included analysis of the rare migraine subtype, familial hemiplegic migraine with several causal genes identified for this severe subtype. However, the exact genetic contributors to the more common migraine subtypes are still to be deciphered. Genome-wide studies such as genome-wide association studies and linkage analysis as well as candidate genes studies have been employed to investigate genes involved in common migraine. Neurological, hormonal and vascular genes are all considered key factors in the pathophysiology of migraine and are a focus of many of these studies. It is clear that the influence of individual genes on the expression of this disorder will vary. Furthermore, the disorder may be dependent on gene--gene and gene--environment interactions that have not yet been considered. In addition, identifying susceptibility genes may require phenotyping methods outside of the International Classification of Headache Disorders II criteria, such as trait component analysis and latent class analysis to better define the ambit of migraine expression.

13 Review Genetics of menstrual migraine: the molecular evidence. 2010

Colson, Natalie / Fernandez, Francesca / Griffiths, Lyn. ·Genomics Research Centre, Griffith Health Institute, School of Medical Science, Griffith University, Gold Coast, Queensland, 4222, Australia. ·Curr Pain Headache Rep · Pubmed #20625856.

ABSTRACT: Migraine is considered to be a multifactorial disorder in which genetic, environmental, and, in the case of menstrual and menstrually related migraine, hormonal events influence the phenotype. Certainly, the role of female sex hormones in migraine has been well established, yet the mechanism behind this well-known relationship remains unclear. This review focuses on the potential role of hormonally related genes in migraine, summarizes results of candidate gene studies to date, and discusses challenges and issues involved in interpreting hormone-related gene results. In light of the molecular evidence presented, we discuss future approaches for analysis with the view to elucidate the complex genetic architecture that underlies the disorder.

14 Article Molecular genetic overlap between migraine and major depressive disorder. 2018

Yang, Yuanhao / Zhao, Huiying / Boomsma, Dorret I / Ligthart, Lannie / Belin, Andrea C / Smith, George Davey / Esko, Tonu / Freilinger, Tobias M / Hansen, Thomas Folkmann / Ikram, M Arfan / Kallela, Mikko / Kubisch, Christian / Paraskevi, Christofidou / Strachan, David P / Wessman, Maija / Anonymous2051131 / van den Maagdenberg, Arn M J M / Terwindt, Gisela M / Nyholt, Dale R. ·Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. y.yang@imb.uq.edu.au. · Institute of Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. y.yang@imb.uq.edu.au. · Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. · Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. · Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands. · Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK. · Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA. · Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. · Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany. · Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. · Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Population Health Research Institute, St George's, University of London, London, UK. · Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. · Folkhälsan Institute of Genetics, Helsinki, Finland. · Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. · Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. d.nyholt@qut.edu.au. ·Eur J Hum Genet · Pubmed #29995844.

ABSTRACT: Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h

15 Article The NRP1 migraine risk variant shows evidence of association with menstrual migraine. 2018

Pollock, Charmaine E / Sutherland, Heidi G / Maher, Bridget H / Lea, Rodney A / Haupt, Larisa M / Frith, Alison / Anne MacGregor, E / Griffiths, Lyn R. ·Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. · Clinithink Limited, Bridgend, UK. · Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, London, UK. · Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. lyn.griffiths@qut.edu.au. ·J Headache Pain · Pubmed #29671086.

ABSTRACT: BACKGROUND: In 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38. While sub-type analysis for migraine without aura (MO) and migraine with aura (MA) found some loci showed specificity to MO, the study did not test the loci with respect to other subtypes of migraine. This study aimed to test the hypothesis that single nucleotide polymorphisms (SNPs) robustly associated with migraine are individually or collectively associated with menstrual migraine (MM). METHODS: Genotyping of migraine susceptibility SNPs was conducted using the Agena MassARRAY platform on DNA samples from 235 women diagnosed with menstrual migraine as per International Classification for Headache Disorders II (ICHD-II) criteria and 140 controls. Alternative genotyping methods including restriction fragment length polymorphism, pyrosequencing and Sanger sequencing were used for validation. Statistical analysis was performed using PLINK and SPSS. RESULTS: Genotypes of 34 SNPs were obtained and investigated for their potential association with menstrual migraine. Of these SNPs, rs2506142 located near the neuropilin 1 gene (NRP1), was found to be significantly associated with menstrual migraine (p = 0.003). Genomic risk scores were calculated for all 34 SNPs as well as a subset of 7 SNPs that were nearing individual significance. Overall, this analysis suggested these SNPs to be weakly predictive of MM, but of no prognostic or diagnostic value. CONCLUSIONS: Our results suggest that NRP1 may be important in the etiology of MM. It also suggests some genetic commonality between common migraine subtypes (MA and MO) and MM. The identification of associated SNPs may be the starting point to a better understanding of how genetic factors may contribute to the menstrual migraine sub-type.

16 Article Genome-wide DNA methylation profiling in whole blood reveals epigenetic signatures associated with migraine. 2018

Gerring, Zachary F / McRae, Allan F / Montgomery, Grant W / Nyholt, Dale R. ·Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. zac.gerring@gmail.com. · Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. · The Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. · Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. ·BMC Genomics · Pubmed #29357833.

ABSTRACT: BACKGROUND: Migraine is a common heritable neurovascular disorder typically characterised by episodic attacks of severe pulsating headache and nausea, often accompanied by visual, auditory or other sensory symptoms. Although genome-wide association studies have identified over 40 single nucleotide polymorphisms associated with migraine, there remains uncertainty about the casual genes involved in disease pathogenesis and how their function is regulated. RESULTS: We performed an epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in 67 migraine cases and 67 controls with a matching age and sex distribution. Association analyses between migraine and methylation probe expression, after adjustment for cell type proportions, indicated an excess of small P values, but there was no significant single-probe association after correction for multiple testing (P < 1.09 × 10 CONCLUSIONS: This study represents the first genome-wide analysis of DNA methylation in migraine. We have identified DNA methylation in the whole blood of subjects associated with migraine, highlighting novel loci that provide insight into the biological pathways and mechanisms underlying migraine pathogenesis.

17 Article Genome-wide analysis of blood gene expression in migraine implicates immune-inflammatory pathways. 2018

Gerring, Zachary F / Powell, Joseph E / Montgomery, Grant W / Nyholt, Dale R. ·1 Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. · 2 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. · 3 The Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. ·Cephalalgia · Pubmed #28058943.

ABSTRACT: Background Typical migraine is a frequent, debilitating and painful headache disorder with an estimated heritability of about 50%. Although genome-wide association (GWA) studies have identified over 40 single nucleotide polymorphisms associated with migraine, further research is required to determine their biological role in migraine susceptibility. Therefore, we performed a study of genome-wide gene expression in a large sample of 83 migraine cases and 83 non-migraine controls to determine whether altered expression levels of genes and pathways could provide insights into the biological mechanisms underlying migraine. Methods We assessed whole blood gene expression data for 17994 expression probes measured using IlluminaHT-12 v4.0 BeadChips. Differential expression was assessed using multivariable logistic regression. Gene expression probes with a nominal p value < 0.05 were classified as differentially expressed. We identified modules of co-regulated genes and tested them for enrichment of differentially expressed genes and functional pathways using a false discovery rate <0.05. Results Association analyses between migraine and probe expression levels, adjusted for age and gender, revealed an excess of small p values, but there was no significant single-probe association after correction for multiple testing. Network analysis of pooled expression data identified 10 modules of co-expressed genes. One module harboured a significant number of differentially expressed genes and was strongly enriched with immune-inflammatory pathways, including multiple pathways expressed in microglial cells. Conclusions These data suggest immune-inflammatory pathways play an important role in the pathogenesis, manifestation, and/or progression of migraine in some patients. Furthermore, gene-expression associations are measurable in whole blood, suggesting the analysis of blood gene expression can inform our understanding of the biological mechanisms underlying migraine, identify biomarkers, and facilitate the discovery of novel pathways and thus determine new targets for drug therapy.

18 Article RE: Six novel rare non-synonymous mutations for migraine without aura identified by exome sequencing. 2017

Albury, Cassie L / Gerring, Zachary F / Griffiths, Lyn R / Nyholt, Dale R / Rodriguez-Acevedo, Astrid J. ·a Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane , Australia. · b Statistical and Genomic Epidemiology Laboratory , Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane , Australia. · c Xavier University School of Medicine , Oranjestad , Aruba. ·J Neurogenet · Pubmed #29105529.

ABSTRACT: -- No abstract --

19 Article Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants. 2017

Winsvold, Bendik S / Bettella, Francesco / Witoelar, Aree / Anttila, Verneri / Gormley, Padhraig / Kurth, Tobias / Terwindt, Gisela M / Freilinger, Tobias M / Frei, Oleksander / Shadrin, Alexey / Wang, Yunpeng / Dale, Anders M / van den Maagdenberg, Arn M J M / Chasman, Daniel I / Nyholt, Dale R / Palotie, Aarno / Andreassen, Ole A / Zwart, John-Anker / Anonymous750921. ·FORMI and Department of Neurology, Oslo University Hospital, Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. · Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. · Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. · Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry Massachusetts General Hospital, Boston, Massachusetts, United States of America. · Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. · Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. · Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. · Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany. · Center for Multimodal Imaging & Genetics, University of California, San Diego, La Jolla, California, United States of America. · Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands. · Harvard Medical School, Boston, Massachusetts, United States of America. · Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Australia. ·PLoS One · Pubmed #28957430.

ABSTRACT: Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10-5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders.

20 Article Electronic-Diary for Recording Headaches, Triggers, and Medication Use: Development and Evaluation. 2017

Bandarian-Balooch, Siavash / Martin, Paul R / McNally, Brenton / Brunelli, Arissa / Mackenzie, Sharon. ·School of Applied Psychology, Griffith University, Southport, Queensland, Australia; Menzies Health Institute Queensland, Gold Coast, Queensland, Australia. ·Headache · Pubmed #28925498.

ABSTRACT: OBJECTIVE: To evaluate an e-diary developed for measuring headaches, triggers, and medication consumption, in terms of reliability and validity, and variables such as ease of use and participant compliance. BACKGROUND: For many decades, behavioral treatment of headaches has been evaluated via participants completing paper diaries recording their headaches and associated phenomena. There is some limited evidence supporting the reliability and validity of paper diaries, and criticisms have been offered such as the large amount of effort involved for both participants and researchers. This study evaluates a new e-diary that will operate on virtually any device that can connect to the internet, and yields 5 of the recommended outcome measures. METHODS: One hundred and eighty-one participants (146 females, 35 males) were allocated to 2 groups, e-diaries vs paper diaries, via a disproportionate stratified allocation process. The e-diary group included 4 subgroups based on the technology available to the participant, and the paper diary group included 2 subgroups, one parallel to the e-dairies (short paper), and one representative of traditional paper diaries (long paper). The study commenced with individuals who had self-identified as headache and migraine sufferers attending a screening session that included headache diagnosis. Participants who met selection criteria then completed the Headache Disability Inventory and a measure of quality of life (SF-36) to assess the convergent validity of the diaries, and the Depression Anxiety Stress Scales to assess the discriminant validity of the diaries. They also completed a Measure of Acceptance Questionnaire. Participants then completed the headache diaries over the next 30 days. Finally, participants completed for a second time the questionnaires completed previously. RESULTS: The 5 outcome measures - headache frequency, peak intensity, average intensity, duration, and medication usage - were found to have strong test-retest reliability (r, 0.68-0.79), for all 3 types of diary. These 5 measures for the e-diaries were shown to have good convergent validity via comparison with scores on the Headache Disability Inventory (r, 0.46-0.55) and SF-36 (r, -0.35 to -0.49), and divergent validity via comparison with scores on the Depression Anxiety and Stress Scale (r, 0.10-0.25). The long-paper diaries had significantly higher missing data scores (M = 15.20, SD = 14.84) and more errors in data completion (M = 5.47, SD = 3.28) than the e-diaries and short-paper diaries (P < .05). In addition, the long-paper diaries were evaluated by the participants as more burdensome and significantly less easy to use than the e-diaries and short-paper diaries. CONCLUSIONS: The e-diaries evaluated in this research would prove a useful tool in clinical trials of behavioral treatment for headaches.

21 Article Body composition status and the risk of migraine: A meta-analysis. 2017

Gelaye, Bizu / Sacco, Simona / Brown, Wendy J / Nitchie, Haley L / Ornello, Raffaele / Peterlin, B Lee. ·From the Harvard T.H. Chan School of Public Health (B.G.), Department of Epidemiology, Boston, MA · Department of Neurology (S.S., R.O.), University of L'Aquila, Italy · School of Human Movement and Nutrition Sciences (W.J.B.), University of Queensland, Brisbane, Australia · and Department of Neurology (H.L.N., B.L.P.), Johns Hopkins University School of Medicine, Baltimore, MD. ·Neurology · Pubmed #28404807.

ABSTRACT: OBJECTIVE: To evaluate the association between migraine and body composition status as estimated based on body mass index and WHO physical status categories. METHODS: Systematic electronic database searches were conducted for relevant studies. Two independent reviewers performed data extraction and quality appraisal. Odds ratios (OR) and confidence intervals (CI) were pooled using a random effects model. Significant values, weighted effect sizes, and tests of homogeneity of variance were calculated. RESULTS: A total of 12 studies, encompassing data from 288,981 unique participants, were included. The age- and sex-adjusted pooled risk of migraine in those with obesity was increased by 27% compared with those of normal weight (odds ratio [OR] 1.27; 95% confidence interval [CI] 1.16-1.37, CONCLUSIONS: The current body of evidence shows that the risk of migraine is increased in obese and underweight individuals. Studies are needed to confirm whether interventions that modify obesity status decrease the risk of migraine.

22 Article Triptan use in Australia 1997-2015: A pharmacoepidemiological study. 2017

Eyre, B L K D / Eadie, M J / van Driel, M L / Ross-Lee, L / Hollingworth, S A. ·School of Pharmacy, The University of Queensland, Woolloongabba, Qld, Australia. · School of Medicine, The University of Queensland, Herston, Qld, Australia. · Department of Pharmacy, Royal Brisbane and Women's Hospital, Herston, Qld, Australia. ·Acta Neurol Scand · Pubmed #28093722.

ABSTRACT: OBJECTIVE: This study examined the use of triptan derivatives in Australia between 1997 and 2015, based on a national drug reimbursement database, and compared patterns of use with available international data. METHODS: We obtained publically available data on the number of prescriptions for triptans marketed in Australia (sumatriptan, eletriptan, rizatriptan, zolmitriptan, naratriptan). Dispensed use was measured as defined daily dose (DDD per 1000 population per day) for Australia's concessional beneficiaries (low-income earners, people with disabilities, and seniors). RESULTS: Total triptan use increased at an average annual rate of 112% over the 18-year period. Sumatriptan was the preferred triptan throughout (average annual increase 45%). Zolmitriptan and naratriptan use peaked in 2004, then decreased. Rizatriptan and eletriptan became available in 2010. There were 3.2-fold and 5.9-fold annual increases in their use from 2011 to 2105. There was some evidence suggesting that pattern of triptan use in concessional beneficiaries probably reflected pattern of overall triptan use in Australia. CONCLUSIONS: The use of triptan derivatives in Australia per head of population for treating migraine attacks continued to increase over the 18-year period studied, with use of recently introduced derivatives more than substituting for decreased use of older triptans. This suggests that the available treatments of migraine attacks had achieved what were considered less than adequate therapeutic outcomes.

23 Article Investigation of polymorphisms in genes involved in estrogen metabolism in menstrual migraine. 2017

Sutherland, Heidi G / Champion, Morgane / Plays, Amelie / Stuart, Shani / Haupt, Larisa M / Frith, Alison / MacGregor, E Anne / Griffiths, Lyn R. ·Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. · Clinithink Limited, Bridgend, UK. · Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science, London, UK. · Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. Electronic address: lyn.griffiths@qut.edu.au. ·Gene · Pubmed #28089731.

ABSTRACT: Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism. Functional polymorphisms in these genes can influence estrogen levels and therefore may be associated with risk of menstrual migraine. In this study we investigated four single nucleotide polymorphisms in three genes involved in estrogen metabolism that have been reported to impact enzyme levels or function, in a specific menstrual migraine cohort. 268 menstrual migraine cases and 142 controls were genotyped for rs4680 in COMT (Val158Met), rs4646903 and rs1048943 in CYP1A1 (T3801C and Ile462Val) and rs700519 in CYP19A1 (Cys264Arg). Neither genotype nor allele frequencies for the COMT and CYP SNPs genotyped were found to be significantly different between menstrual migraineurs and controls by chi-square analysis (P>0.05). Therefore we did not find association of functional polymorphisms in the estrogen metabolism genes COMT, CYP1A1 or CYP19A1 with menstrual migraine. Further studies are required to assess whether menstrual migraine is genetically distinct from the common migraine subtypes and identify genes that influence risk.

24 Article Acute Headache Presentations to the Emergency Department: A Statewide Cross-sectional Study. 2017

Chu, Kevin H / Howell, Tegwen E / Keijzers, Gerben / Furyk, Jeremy S / Eley, Robert M / Kinnear, Frances B / Thom, Ogilvie / Mahmoud, Ibrahim / Brown, Anthony F T. ·School of Medicine, University of Queensland, Herston, Queensland, Australia. · Department of Emergency Medicine, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia. · School of Medicine, Griffith University, Nathan, Queensland, Australia. · School of Medicine, Bond University, Gold Coast, Queensland, Australia. · Department of Emergency Medicine, Gold Coast University Hospital, Gold Coast, Queensland, Australia. · College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. · Department of Emergency Medicine, The Townsville Hospital, Townsville, Queensland, Australia. · Department of Emergency Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia. · Department of Emergency Medicine, The Prince Charles Hospital, Brisbane, Queensland, Australia. · Department of Emergency Medicine, Nambour General Hospital, Nambour, Queensland, Australia. ·Acad Emerg Med · Pubmed #27473746.

ABSTRACT: OBJECTIVES: The objective of this study was to describe demographic and clinical characteristics including features that were consistent with subarachnoid hemorrhage (SAH), use of diagnostic tests, emergency department (ED) discharge diagnoses, and disposition of adult patients presenting with an acute headache to EDs statewide across Queensland, Australia. In addition, potential variations in the presentation and diagnostic workup between principal-referral and city-regional hospitals were examined. METHODS: A prospective cross-sectional study was conducted over 4 weeks in September 2014. All patients ≥ 18 years presenting to one of 29 public and five private hospital EDs across the state with an acute headache were included. The headache had to be the principal presenting complaint and nontraumatic. The 34 study sites attend to about 90% of all ED presentations statewide. The treating doctor collected clinical information at the time of the ED visit including the characteristics of the headache and investigations performed. A study coordinator retrieved results of investigations, ED discharge diagnoses, and disposition from state databases. Variations in presentation, investigations, and diagnosis between city-regional and principal-referral hospitals were examined. RESULTS: There were 847 headache presentations. Median (range) age was 39 (18-92) years, 62% were female, and 31% arrived by ambulance. Headache peaked instantly in 18% and ≤ 1 hour in 44%. It was "worst ever" in 37%, 10/10 in severity in 23%, and associated with physical activity in 7.4%. Glasgow Coma Scale score was < 15 in 4.1%. Neck stiffness was noted on examination in 4.8%. Neurologic deficit persisting in the ED was found in 6.5%. A computed tomography (CT) head scan was performed in 38% (318/841, 95% CI = 35% to 41%) and an lumbar puncture in 4.7% (39/832, 95% CI = 3.4% to 6.3%). There were 18 SAH, six intraparenchymal hemorrhages, one subdural hematoma, one newly diagnosed brain metastasis, and two bacterial meningitis. Migraine was diagnosed in 23% and "primary headache not further specified" in 45%. CT head scans were more likely to be performed in principal-referral hospitals (41%) compared to city-regional hospitals (33%). The headache in patients presenting to the latter was less likely to be instantly peaking or associated with activity, but was no less severe in intensity and was more frequently accompanied by nausea and vomiting. Their diagnosis was more likely to be a benign primary headache. Variations in CT scanning could thus be due to differences in the case mix. The median (interquartile range) ED length of stay was 3.1 (2.2 to 4.5) hours. Patients was discharged from the ED or admitted to the ED short-stay unit prior to discharge in 57 and 23% of cases, respectively. CONCLUSIONS: The majority of patients had a benign diagnosis, with intracranial hemorrhage and bacterial meningitis accounting for only 3% of the diagnoses. There are variations in the proportion of patients receiving CT head scans between city-regional and principal-referral hospitals. As 38% of headache presentations overall underwent CT scanning, there is scope to rationalize diagnostic testing to rule out life-threatening conditions.

25 Article Migraine genetics: from genome-wide association studies to translational insights. 2016

Gormley, Padhraig / Winsvold, Bendik S / Nyholt, Dale R / Kallela, Mikko / Chasman, Daniel I / Palotie, Aarno. ·Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. pgormley@broadinstitute.org. · Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. pgormley@broadinstitute.org. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. pgormley@broadinstitute.org. · FORMI, Oslo University Hospital, PO 4956, Nydalen, 0424, Oslo, Norway. · Department of Neurology, Oslo University Hospital, PO 4956, Nydalen, 0424, Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, PO 1171, Blindern, 0318, Oslo, Norway. · Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD, 4059, Australia. · Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA. · Harvard Medical School, Boston, MA, 02115, USA. · Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. · Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. · Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. · Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014, Helsinki, Finland. · Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA. ·Genome Med · Pubmed #27543003.

ABSTRACT: -- No abstract --

Next