Genetic variability in the regulation of gene expression in ten regions of the human brain.
Nat Neurosci, 2014/10;17(10):1418-1428.
Ramasamy A[1, 2], Trabzuni D[2, 3], Guelfi S[2], Varghese V[1], Smith C[4], Walker R[4], De T[5], UK Brain Expression Consortium, North American Brain Expression Consortium, Coin L[6], de Silva R[2], Cookson MR[7], Singleton AB[7], Hardy J[2], Ryten M[1, 2], Weale ME[1]
Affiliations
PMID: 25174004DOI: 10.1038/nn.3801
Impact factor: 28.771
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.
MeSH terms
Adolescent; Adult; Aged; Aged, 80 and over; Brain; Female; Gene Expression Profiling; Gene Expression Regulation; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Nervous System Diseases; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Young Adult
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download