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.
authors.affiliation: Department of Medical & Molecular Genetics, King's College London, Guy's Hospital, London, UK.|Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: Adaikalavan
authors.initials: A
authors.lastname: Ramasamy
authors.affiliation: Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.|Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Daniah
authors.initials: D
authors.lastname: Trabzuni
authors.affiliation: Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Guelfi
authors.affiliation: Department of Medical & Molecular Genetics, King's College London, Guy's Hospital, London, UK.
authors.forename: Vibin
authors.initials: V
authors.lastname: Varghese
authors.affiliation: Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Walker
authors.affiliation: School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Tisham
authors.initials: T
authors.lastname: De
authors.affiliation: Institute of Molecular Bioscience, The University of Queensland, Brisbane St Lucia, Queensland, Australia.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Coin
authors.affiliation: Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Department of Medical & Molecular Genetics, King's College London, Guy's Hospital, London, UK.|Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: Mina
authors.initials: M
authors.lastname: Ryten
authors.affiliation: Department of Medical & Molecular Genetics, King's College London, Guy's Hospital, London, UK.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D055815:Young Adult