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Nat Neurosci. 2014 Oct;17(10):1418-1428. doi: 10.1038/nn.3801. Epub 2014 Aug 31.

Genetic variability in the regulation of gene expression in ten regions of the human brain.

Author information

1
Department of Medical & Molecular Genetics, King's College London, Guy's Hospital, London, UK.
2
Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
3
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
4
Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh, UK.
5
School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
6
Institute of Molecular Bioscience, The University of Queensland, Brisbane St Lucia, Queensland, Australia.
7
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
#
Contributed equally

Abstract

Germ-line genetic control of gene expression occurs via expression quantitative trait loci (eQTLs). We present a large, exon-specific eQTL data set covering ten human brain regions. We found that cis-eQTL signals (within 1 Mb of their target gene) were numerous, and many acted heterogeneously among regions and exons. Co-regulation analysis of shared eQTL signals produced well-defined modules of region-specific co-regulated genes, in contrast to standard coexpression analysis of the same samples. We report cis-eQTL signals for 23.1% of catalogued genome-wide association study hits for adult-onset neurological disorders. The data set is publicly available via public data repositories and via http://www.braineac.org/. Our study increases our understanding of the regulation of gene expression in the human brain and will be of value to others pursuing functional follow-up of disease-associated variants.

PMID:
25174004
PMCID:
PMC4208299
DOI:
10.1038/nn.3801
[Indexed for MEDLINE]
Free PMC Article

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