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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.
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“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]
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Additional file 1 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.22608512
Additional file 2 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.22608515
Additional file 10 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.22608542
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
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