Journal article
Genetic variability in the regulation of gene expression in ten regions of the human brain
A Ramasamy, D Trabzuni, S Guelfi, V Varghese, C Smith, R Walker, T De, L Coin, R De Silva, MR Cookson, AB Singleton, J Hardy, M Ryten, ME Weale
Nature Neuroscience | NATURE PUBLISHING GROUP | Published : 2014
DOI: 10.1038/nn.3801
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 h..
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Awarded by King’s College London
Funding Acknowledgements
We are grateful to the Banner Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for the provision of human biospecimens. The Brain and Body Donation Program is supported by the US National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson's Research. We would like to thank AROS Applied Biotechnology AS company laboratories and Affymetrix for their input. H. Jonvik, L. Stanyer, J. Toombs and M. Gaskin provided invaluable assistance in helping with Our computer infrastructure and in sample handling and databasing. We thank A. Pittman for discussions. This work was supported by the UK Medical Research Council (MRC) through the MRC Sudden Death Brain Bank (C.S.), a Project Grant (G0901254 to J.H. and M.E.W) and Training Fellowship (G0802462 to M.R.). D.T. was supported by the King Faisal Specialist Hospital and Research Centre, Saudi Arabia. This work was also supported in part by the Intramural Research Program of the US National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project ZO1 AG000947. We acknowledge support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.