A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese

Jiang, Teng; Tan, Lan; Chen, Qi; Tan, Meng-Shan; Zhou, Jun-Shan; Zhu, Xi-Chen; Lu, Huan; Wang, Hui-Fu; Zhang, Ying-Dong; Yu, Jin-Tai

doi:10.1016/j.neurobiolaging.2016.02.023

Cited by 110Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese

Jiang, Teng, Tan, Lan, Chen, Qi, Tan, Meng-Shan, Zhou, Jun-Shan, Zhu, Xi-Chen, Lu, Huan, Wang, Hui-Fu +2 more·2016·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2016.02.023

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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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TREM2 variants associate with an increased risk of AD.
“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]
Genetic studies in East Asian populations have been unable to replicate the significance of the TREM2 p.R47H variant because it is rarely found in this population.
“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]
The significance of TREM2 p.H157Y has been confirmed in the Chinese population.
“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]
TREM2 p.H157Y (rs2234255) has been detected in Caucasians, Chinese, and Japanese.
“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]
To date, thousands of Chinese and Japanese have been screened for the TREM2 p.R47H variant, and only three Japanese carriers have been reported.
“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]

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Additional file 1 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
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Additional file 2 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
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Additional file 10 of Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology
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A rare coding variant in TREM2 increases risk for Alzheimer’s disease in Han Chinese (P5.164)
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Identification of a rare coding variant in TREM2 in a Chinese individual with Alzheimer’s disease
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Coding variants in TREM2 increase risk for Alzheimer's disease
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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
ORCID: Jiang, Teng
Tan, Lan
Chen, Qi
Tan, Meng-Shan
Zhu, Xi-Chen
Lu, Huan
Wang, Hui-Fu
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)
DOI: 10.1016/j.neurobiolaging.2016.02.023
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › 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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A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese

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