We have explored the associations between DNA variants in the genome, particularly single nucleotide polymorphisms (SNPs) and expression of nearby mRNA. At a genome wide level, there are many such associations found as expression quantitative trait loci (eQTLs). We have generated, and made publically available, one of the largest eQTL mapping sets in the human brain, with nearly 400 individuals with age range covering most of the human lifespan where genotype and expression data form microarrays is available. Primarily this is focused on two brain regions, the cerebellum and the frontal cerebral cortex, with ancillary datasets in other brain regions and on isolated cell types.
Our aim i s to provide a comprehensive view of the genomic control of gene expression in this complex organ that can be examined in a number of ways. We have examined the role of genetic variation in gene expression in a number of analyses over the past reporting period. For example, we have shown that while there is overlap in eQTLs between blood and brain there are also distinct differences that are not easily explained by gene expression levels. Ongoing analyses include an investigation into the relationship of age and expression in human brain. We are also moving these analyses forward to use novel techniques for measuring mRNA expression, including RNA-sequencing. As in prior reporting, we have seen these datasets used by other groups, particularly those interesting in genetic variation associated with neurological and psychiatric conditions. Several publications have resulted from the use of this publicly available resource.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Institute on Aging
Zip Code
Cookson, Mark R (2017) RNA-binding proteins implicated in neurodegenerative diseases. Wiley Interdiscip Rev RNA 8:
Dillman, Allissa A; Cookson, Mark R; Galter, Dagmar (2016) ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicing in vivo. RNA Biol 13:15-24
Blauwendraat, Cornelis; Francescatto, Margherita; Gibbs, J Raphael et al. (2016) Comprehensive promoter level expression quantitative trait loci analysis of the human frontal lobe. Genome Med 8:65
Hibar, Derrek P (see original citation for additional authors) (2015) Common genetic variants influence human subcortical brain structures. Nature 520:224-9
Ramasamy, Adaikalavan; Trabzuni, Daniah; Guelfi, Sebastian et al. (2014) Genetic variability in the regulation of gene expression in ten regions of the human brain. Nat Neurosci 17:1418-1428
Nalls, Mike A; Saad, Mohamad; Noyce, Alastair J et al. (2014) Genetic comorbidities in Parkinson's disease. Hum Mol Genet 23:831-41
Dillman, Allissa A; Cookson, Mark R (2014) Transcriptomic changes in brain development. Int Rev Neurobiol 116:233-50
Johnson, Janel O; Pioro, Erik P; Boehringer, Ashley et al. (2014) Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nat Neurosci 17:664-666
Ramasamy, Adaikalavan; Trabzuni, Daniah; Gibbs, J Raphael et al. (2013) Resolving the polymorphism-in-probe problem is critical for correct interpretation of expression QTL studies. Nucleic Acids Res 41:e88
Majounie, Elisa; Cross, William; Newsway, Victoria et al. (2013) Variation in tau isoform expression in different brain regions and disease states. Neurobiol Aging 34:1922.e7-1922.e12

Showing the most recent 10 out of 27 publications