Minerva Carrasquillo
A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression
Carrasquillo, Minerva; Allen, Mariet; Burgess, Jeremy D.; Medway, Christopher; Morgan, Kevin
Authors
Mariet Allen
Jeremy D. Burgess
Christopher Medway
Kevin Morgan
Abstract
Introduction: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression.
Methods: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis.
Results: A variant within a DNase hypersensitive site 5′ of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni-corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively).
Discussion: Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD.
Citation
Carrasquillo, M., Allen, M., Burgess, J. D., Medway, C., & Morgan, K. (2017). A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 13(6), https://doi.org/10.1016/j.jalz.2016.10.005
Journal Article Type | Article |
---|---|
Acceptance Date | Dec 8, 2016 |
Online Publication Date | Dec 8, 2016 |
Publication Date | Jun 1, 2017 |
Deposit Date | Dec 16, 2016 |
Publicly Available Date | Dec 16, 2016 |
Journal | Alzheimer's & Dementia |
Print ISSN | 1552-5260 |
Electronic ISSN | 1552-5279 |
Publisher | Wiley Open Access |
Peer Reviewed | Peer Reviewed |
Volume | 13 |
Issue | 6 |
DOI | https://doi.org/10.1016/j.jalz.2016.10.005 |
Keywords | Alzheimer's disease; eQTL; TREM2; TREML1; Regulatory variant |
Public URL | https://nottingham-repository.worktribe.com/output/968282 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S1552526016330710 |
Contract Date | Dec 16, 2016 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0
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