SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

Eising, E; Huisman, SM; Mahfouz, A; Vijfhuizen, LS; Anttila, V; Winsvold, BS; Kurth, T; Ikram, MA; Freilinger, T; Kaprio, J; et al. Eising, E; Huisman, SM; Mahfouz, A; Vijfhuizen, LS; Anttila, V; Winsvold, BS; Kurth, T; Ikram, MA; Freilinger, T; Kaprio, J; Boomsma, DI; van Duijn, CM; Järvelin, MR; Zwart, JA; Quaye, L; Strachan, DP; Kubisch, C; Dichgans, M; Davey Smith, G; Stefansson, K; Palotie, A; Chasman, DI; Ferrari, MD; Terwindt, GM; de Vries, B; Nyholt, DR; Lelieveldt, BP; van den Maagdenberg, AM; Reinders, MJ (2016) Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas. Human Genetics, 135 (4). pp. 425-439. https://doi.org/10.1007/s00439-016-1638-x
SGUL Authors: Strachan, David Peter

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (8MB) | Preview

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.

Item Type: Article
Additional Information: © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons. org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Genetics & Heredity, 0604 Genetics, 1104 Complementary And Alternative Medicine, 1114 Paediatrics And Reproductive Medicine
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Human Genetics
Language: ENG
Dates:
DateEvent
22 February 2016Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
602633Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
604102Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
PubMed ID: 26899160
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107772
Publisher's version: https://doi.org/10.1007/s00439-016-1638-x

Actions (login required)

Edit Item Edit Item