The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese
Abstract
Two recent studies have identified that a rare coding variant (p.R47H) in exon 2 of triggering receptor expressed on myeloid cells 2 (TREM2) gene is associated with Alzheimer's disease (AD) susceptibility in Caucasians. This association was not successfully replicated in Han Chinese, where this variant was rare or even absent. Previously, we resequenced TREM2 exon 2 to investigate whether additional rare variants conferred risk to AD in our cohort. Although several new variants had been identified, none of them was significantly associated with disease susceptibility. Here, to test whether TREM2 is truly a susceptibility gene of AD in Han Chinese, we extend our previous study by sequencing the other four exons of TREM2 in 988 AD patients and 1,354 healthy controls. We provided the first evidence that a rare coding variant (p.H157Y) in TREM2 exon 3 conferred a considerable risk of AD in our cohort (Pcorrected = 0.02, odds ratio = 11.01, 95% confidence interval: 1.38-88.05). This finding indicates that rare coding variants of TREM2 may play an important role in AD in Han Chinese.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Importantly, TREM2 variants associate with an increased risk of AD [15, 25, 38–40].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [39]
In the citing paper
“However, genetic studies in East Asian populations have been unable to replicate the significance of the p.R47H variant in TREM2, because it is rarely found in this population.”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [40]
In the citing paper
“For example, TREM2 p.H157Y (rs2234255) has been detected not only in Caucasians [35] but also in Chinese [40] and Japanese [24], and the significance of this variant has been confirmed in the Chinese population (Table 4) [40].”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [40]
In the citing paper
“For example, TREM2 p.H157Y (rs2234255) has been detected not only in Caucasians [35] but also in Chinese [40] and Japanese [24], and the significance of this variant has been confirmed in the Chinese population (Table 4) [40].”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [40]
In the citing paper
“To date, thousands of Chinese and Japanese have been screened for p.R47H variant, and only three Japanese carriers of this variant have been reported (Table 4) [38–42].”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [40]
In the citing paper
“Several other TREM2 variants that affect the expression of TREM2 also increased the risk of AD, including R62H, T66M, H157Y, and D87N.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [167]
In the citing paper
“In addition to the R47H variant, further TREM2 variants have been revealed to be risk factors of AD or other CNS diseases, such as R62H (8,20), H157Y (25), Q33X, T66M and Y38C (26,27).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [25]
Citations
Cites
TREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.049 · Cited by 1,736
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009093 · Cited by 798
Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142322 · Cited by 682 · cited 1×
“Under AD condition, TREM2 was revealed to exert a protective effect by enhancement of Ab clearance and suppression of inflammatory response (Wang et al., 2015), although the opposite result was reported by Jay et al. (2015).”
ResultApolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679043 · Cited by 587
TREM2 sustains microglial expansion during aging and response to demyelination
Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S., & Colonna, M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77983 · Cited by 525
Kawabori, M., Kacimi, R., Kauppinen, T., Calosing, C., Kim, J. Y., Hsieh, C. L., Nakamura, M. C., & Yenari, M. A. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2620-14.2015 · Cited by 375
Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status
Piccio, L., Deming, Y., Del-Águila, J. L., Ghezzi, L., Holtzman, D. M., Fagan, A. M., Fenoglio, C., Galimberti, D., Borroni, B., & Cruchaga, C. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1533-5 · Cited by 337
Jiang, T., Tan, L., Zhu, X.-C., Zhang, Q.-Q., Cao, L., Tan, M.-S., Gu, L.-Z., Wang, H.-F., Ding, Z.-Z., Zhang, Y.-D., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.164 · Cited by 320
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–110 of 110
Additional file 7 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
Qiao, W., Chen, Y., Zhong, J., Madden, B. J., Charlesworth, C. M., Martens, Y. A., Liu, C.-C., Knight, J., Ikezu, T. C., Kurti, A., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22608530
Additional file 5 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
Qiao, W., Chen, Y., Zhong, J., Madden, B. J., Charlesworth, C. M., Martens, Y. A., Liu, C.-C., Knight, J., Ikezu, T. C., Kurti, A., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22608524
Additional file 4 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
Qiao, W., Chen, Y., Zhong, J., Madden, B. J., Charlesworth, C. M., Martens, Y. A., Liu, C.-C., Knight, J., Ikezu, T. C., Kurti, A., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22608521
Additional file 3 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
Qiao, W., Chen, Y., Zhong, J., Madden, B. J., Charlesworth, C. M., Martens, Y. A., Liu, C.-C., Knight, J., Ikezu, T. C., Kurti, A., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22608518
Additional file 6 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
Qiao, W., Chen, Y., Zhong, J., Madden, B. J., Charlesworth, C. M., Martens, Y. A., Liu, C.-C., Knight, J., Ikezu, T. C., Kurti, A., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22608527
Additional file 9 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
Qiao, W., Chen, Y., Zhong, J., Madden, B. J., Charlesworth, C. M., Martens, Y. A., Liu, C.-C., Knight, J., Ikezu, T. C., Kurti, A., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22608539
Additional file 8 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
Qiao, W., Chen, Y., Zhong, J., Madden, B. J., Charlesworth, C. M., Martens, Y. A., Liu, C.-C., Knight, J., Ikezu, T. C., Kurti, A., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22608536
Amyloid Beta Revisited: A Versatile Immune PolypeptidePreprint
Slama, P. S. (2026) · Qeios · doi:10.32388/2esvyp
Amyloid Beta Revisited: A Versatile Immune PolypeptidePreprint
Slama, P. S. (2026) · Qeios · doi:10.32388/2esvyp.2
Revisiting the role of amyloid-β: A molecular and immunological perspective
Slama, P. S. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261484863
Metadata
- Authors
- Jiang, T., Tan, L., Chen, Q., Tan, M.-S., Zhou, J.-S., Zhu, X.-C., Lu, H., Wang, H.-F., Zhang, Y.-D., & Yu, J.-T.
- Affiliations
- University of California, San Francisco (US)
- Qingdao University (CN)
- Nanjing Medical University (CN)
- Qingdao Municipal Hospital (CN)
- Corresponding author
- Tan, Lan
- Yu, Jin-Tai
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 42
- Pages
- 217.e1-217.e3
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2292528698
- Cited by
- 110
- References
- 15
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 8 · 2023: 20 · 2022: 7 · 2021: 17 · 2020: 8 · 2019: 10 · 2018: 12 · 2017: 9 · 2016: 1
- FWCI
- 8.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TREM2, Alzheimer's disease, rare coding variants, genetic susceptibility, Han Chinese, exon 3, exon 2, genetic association, myeloid cells
- MeSH terms
- Alzheimer Disease, Exons, Humans, Membrane Glycoproteins, Receptors, Immunologic, Risk, Genetic Variation, Cohort Studies, Genetic Predisposition to Disease, Asian People, Genetic Association Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
