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

UK Brain Expression Consortium; North Amer Brain Expression Consor; Adaikalavan Ramasamy; Daniah Trabzuni; Sebastian Guelfi; Vibin Varghese; Colin Smith; Robert Walker; Tisham De; Lachlan Coin; Rohan de Silva; Mark R. Cookson; Andrew B. Singleton; John Hardy; Mina Ryten; Michael E. Weale

doi:10.1038/nn.3801

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

UK Brain Expression Consortium, North Amer Brain Expression Consor, Adaikalavan Ramasamy, Daniah Trabzuni, Sebastian Guelfi, Vibin Varghese, Colin Smith, Robert Walker, Tisham De, Lachlan Coin, Rohan de Silva, Mark R. Cookson, Andrew B. Singleton, John Hardy, Mina Ryten^*, Michael E. Weale

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1418-1428
Number of pages	11
Journal	Nature Neuroscience
Volume	17
Issue number	10
Early online date	31 Aug 2014
DOIs	https://doi.org/10.1038/nn.3801
Publication status	Published - 31 Oct 2014

Keywords / Materials (for Non-textual outputs)

GENOME-WIDE ASSOCIATION
HUMAN PREFRONTAL CORTEX
ALZHEIMERS-DISEASE
SMOKING-BEHAVIOR
COMMON VARIANTS
LUNG-CANCER
SUSCEPTIBILITY
METAANALYSIS
LOCUS
CD2AP

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10.1038/nn.3801Licence: All Rights Reserved

Colin Smith
- csmith9staffmail.ed.acuk
- Deanery of Clinical Sciences - Personal Chair Neuropathology
- Centre for Clinical Brain Sciences
- Euan MacDonald Centre for Motor Neuron Disease Research
- Edinburgh Neuroscience
- Cerebrovascular Research Group
Person: Academic: Research Active

Cite this

UK Brain Expression Consortium, North Amer Brain Expression Consor, Ramasamy, A., Trabzuni, D., Guelfi, S., Varghese, V., Smith, C., Walker, R., De, T., Coin, L., de Silva, R., Cookson, M. R., Singleton, A. B., Hardy, J., Ryten, M., & Weale, M. E. (2014). Genetic variability in the regulation of gene expression in ten regions of the human brain. Nature Neuroscience, 17(10), 1418-1428. https://doi.org/10.1038/nn.3801

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title = "Genetic variability in the regulation of gene expression in ten regions of the human brain",

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.",

keywords = "GENOME-WIDE ASSOCIATION, HUMAN PREFRONTAL CORTEX, ALZHEIMERS-DISEASE, SMOKING-BEHAVIOR, COMMON VARIANTS, LUNG-CANCER, SUSCEPTIBILITY, METAANALYSIS, LOCUS, CD2AP",

author = "{UK Brain Expression Consortium} and {North Amer Brain Expression Consor} and Adaikalavan Ramasamy and Daniah Trabzuni and Sebastian Guelfi and Vibin Varghese and Colin Smith and Robert Walker and Tisham De and Lachlan Coin and {de Silva}, Rohan and Cookson, {Mark R.} and Singleton, {Andrew B.} and John Hardy and Mina Ryten and Weale, {Michael E.}",

year = "2014",

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doi = "10.1038/nn.3801",

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UK Brain Expression Consortium, North Amer Brain Expression Consor, Ramasamy, A, Trabzuni, D, Guelfi, S, Varghese, V, Smith, C, Walker, R, De, T, Coin, L, de Silva, R, Cookson, MR, Singleton, AB, Hardy, J, Ryten, M & Weale, ME 2014, 'Genetic variability in the regulation of gene expression in ten regions of the human brain', Nature Neuroscience, vol. 17, no. 10, pp. 1418-1428. https://doi.org/10.1038/nn.3801

TY - JOUR

T1 - Genetic variability in the regulation of gene expression in ten regions of the human brain

AU - UK Brain Expression Consortium

AU - North Amer Brain Expression Consor

AU - Ramasamy, Adaikalavan

AU - Trabzuni, Daniah

AU - Guelfi, Sebastian

AU - Varghese, Vibin

AU - Smith, Colin

AU - Walker, Robert

AU - De, Tisham

AU - Coin, Lachlan

AU - de Silva, Rohan

AU - Cookson, Mark R.

AU - Singleton, Andrew B.

AU - Hardy, John

AU - Ryten, Mina

AU - Weale, Michael E.

PY - 2014/10/31

Y1 - 2014/10/31

N2 - 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.

AB - 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.

KW - GENOME-WIDE ASSOCIATION

KW - HUMAN PREFRONTAL CORTEX

KW - ALZHEIMERS-DISEASE

KW - SMOKING-BEHAVIOR

KW - COMMON VARIANTS

KW - LUNG-CANCER

KW - SUSCEPTIBILITY

KW - METAANALYSIS

KW - LOCUS

KW - CD2AP

U2 - 10.1038/nn.3801

DO - 10.1038/nn.3801

M3 - Article

SN - 1097-6256

VL - 17

SP - 1418

EP - 1428

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 10

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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Colin Smith

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