A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression
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 neuropathologi...
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/39400/ |
| _version_ | 1848795828501610496 |
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| author | Carrasquillo, Minerva Allen, Mariet Burgess, Jeremy D. Medway, Christopher Morgan, Kevin |
| author_facet | Carrasquillo, Minerva Allen, Mariet Burgess, Jeremy D. Medway, Christopher Morgan, Kevin |
| author_sort | Carrasquillo, Minerva |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:38:17Z |
| format | Article |
| id | nottingham-39400 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:38:17Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-394002020-05-04T19:56:53Z https://eprints.nottingham.ac.uk/39400/ 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 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. Elsevier 2017-06 Article PeerReviewed Carrasquillo, Minerva, Allen, Mariet, Burgess, Jeremy D., Medway, Christopher and Morgan, Kevin (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, 13 (6). pp. 663-673. ISSN 1552-5260 Alzheimer's disease; eQTL; TREM2; TREML1; Regulatory variant http://www.sciencedirect.com/science/article/pii/S1552526016330710 doi:10.1016/j.jalz.2016.10.005 doi:10.1016/j.jalz.2016.10.005 |
| spellingShingle | Alzheimer's disease; eQTL; TREM2; TREML1; Regulatory variant Carrasquillo, Minerva Allen, Mariet Burgess, Jeremy D. Medway, Christopher Morgan, Kevin A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression |
| title | A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression |
| title_full | A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression |
| title_fullStr | A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression |
| title_full_unstemmed | A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression |
| title_short | A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression |
| title_sort | candidate regulatory variant at the trem gene cluster associates with decreased alzheimer's disease risk and increased treml1 and trem2 brain gene expression |
| topic | Alzheimer's disease; eQTL; TREM2; TREML1; Regulatory variant |
| url | https://eprints.nottingham.ac.uk/39400/ https://eprints.nottingham.ac.uk/39400/ https://eprints.nottingham.ac.uk/39400/ |