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
Jeremy D. Burgess
KEVIN MORGAN firstname.lastname@example.org
Professor of Human Genomics and Molecular Genetics
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.
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 and Dementia, 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|
|Peer Reviewed||Peer Reviewed|
|Keywords||Alzheimer's disease; eQTL; TREM2; TREML1; Regulatory variant|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0
You might also like
Heritability and genetic variance of dementia with Lewy bodies