Genetic Variability in the Regulation of Gene Expression in Ten Regions of the Human Brain

Overview

Journal Nat Neurosci

Date 2014 Sep 1

PMID 25174004

Citations 399

Authors

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

Affiliations

Soon will be listed here.

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.

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