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




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Human Genetics

, Volume 135, Issue 4, pp 425–439

First Online: 22 February 2016Received: 13 November 2015Accepted: 16 January 2016

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.

On behalf of the International Headache Genetics Consortium.

Members of the International Headache Genetics Consortium are listed in Acknowledgements.

Else Eising and Sjoerd M. H. Huisman contributed equally to this work.

Arn M. J. M. van den Maagdenberg, Boudewijn P. F. Lelieveldt, and Marcel J. T. Reinders jointly directed this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00439-016-1638-x contains supplementary material, which is available to authorized users.

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Autor: Else Eising - Sjoerd M. H. Huisman - Ahmed Mahfouz - Lisanne S. Vijfhuizen - Verneri Anttila - Bendik S. Winsvold - Tobi

Fuente: https://link.springer.com/



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