Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas
Year: 2016
Type: article
Abstract: 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.
Source: Human Genetics
Authors: Else Eising, Sjoerd M. H. Huisman, Ahmed Mahfouz, Lisanne S. Vijfhuizen, Verneri Anttila, Bendik S. Winsvold, Tobias Kurth, M. Arfan Ikram, Tobias Freilinger, Jaakko Kaprio, Dorret I. Boomsma, Cornelia M. van Duijn, Marjo-Riitta R. Järvelin, John-Anker Zwart, Lydia Quaye, David P. Strachan, Christian Kubisch, Martin Dichgans, George Davey Smith, Kari Stefansson, Aarno Palotie, Daniel I. Chasman, Michel D. Ferrari, Gisela M. Terwindt, Boukje de Vries, Dale R. Nyholt, Boudewijn P. F. Lelieveldt, Arn M. J. M. van den Maagdenberg, Marcel J. T. Reinders
Institutions: Leiden University Medical Center, Delft University of Technology, Broad Institute, Harvard University, Massachusetts General Hospital, Stanley Center for Psychiatric Research, Oslo University Hospital, University of Oslo, Brigham and Women's Hospital, Charité – Universitätsmedizin Berlin, Erasmus MC, LMU Klinikum, Hertie Institute for Clinical Brain Research, Institut für Schlaganfall- und Demenzforschung, University of Tübingen, Ludwig-Maximilians-Universität München, University of Helsinki, Institute for Molecular Medicine Finland, Vrije Universiteit Amsterdam, Oulu University Hospital, MRC Centre for Environment and Health, Imperial College London, University of Oulu, King's College London, St George's, University of London, University Medical Center Hamburg-Eppendorf, Munich Cluster for Systems Neurology, University of Bristol, MRC Integrative Epidemiology Unit, deCODE Genetics (Iceland), University of Iceland, Queensland University of Technology, QIMR Berghofer Medical Research Institute
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,690
Awards: The Human Brain Project, G1144258087, G1844275805, Mechanisms and Treatment of Migraine and its Chronification, G2138066930, G3445821079, G3987576704, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G4598234423, The Women's Health Study: Infrastructure Support for Continued Cohort Follow-up, G6689231961, G8293913073, G8750896698
OpenAlex ID: W2280484307