Lack of Genetic Association Between TREM2 and Alzheimer’s Disease in East Asian Population

Huang, Man; Wang, Dejun; Xu, Zhifeng; Xu, Yongshan; Xu, Xiaoping; Ma, Yuefeng; Zheng, Xiaojiao

doi:10.1177/1533317515577128

Cited by 22 publications

(17 citation statements)

References 17 publications

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“…References shown in light green did find a significant association between the TREM2 variant and disease risk, but only in one or multiple populations they examined or only after inclusion of previously published literature into metastudy analyses. While these variants have been significantly associated with disease risk, many more studies find suggestive but not significant associations between additional TREM2 variants and NDD risk which are not represented here [ 5 , 6 , 16 , 18 , 26 , 28 , 30 , 31 , 35 – 37 , 39 – 42 , 45 – 47 , 49 – 52 , 54 , 55 , 57 , 58 , 60 , 64 , 65 , 67 , 70 , 82 , 83 , 88 , 131 , 323 – 325 ] …”

Section: Genetics Of Trem2 In Nddsmentioning

confidence: 83%

“…In Caucasian populations, the minor allele frequency (MAF) of the R47H TREM2 variant ranges from 0.12–0.26% in the United States, to up to 2% in some specific British populations [ 5 , 6 , 59 ]. While the R47H variant is virtually absent in East Asian individuals, [ 56 , 69 , 75 – 81 ] nine other TREM2 variants were present in East Asian populations and collectively associated with NDD risk [ 82 ]. Similarly, the MAF of the R47H and R62H variants are much lower in African Americans compared to European American populations [ 83 , 84 ].…”

Section: Genetics Of Trem2 In Nddsmentioning

confidence: 99%

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TREM2 in Neurodegenerative Diseases

Jay

Saucken

Landreth

2017

Mol Neurodegeneration

304

283

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TREM2 variants have been identified as risk factors for Alzheimer's disease (AD) and other neurodegenerative diseases (NDDs). Because TREM2 encodes a receptor exclusively expressed on immune cells, identification of these variants conclusively demonstrates that the immune response can play an active role in the pathogenesis of NDDs. These TREM2 variants also confer the highest risk for developing Alzheimer's disease of any risk factor identified in nearly two decades, suggesting that understanding more about TREM2 function could provide key insights into NDD pathology and provide avenues for novel immune-related NDD biomarkers and therapeutics. The expression, signaling and function of TREM2 in NDDs have been extensively investigated in an effort to understand the role of immune function in disease pathogenesis and progression. We provide a comprehensive review of our current understanding of TREM2 biology, including new insights into the regulation of TREM2 expression, and TREM2 signaling and function across NDDs. While many open questions remain, the current body of literature provides clarity on several issues. While it is still often cited that TREM2 expression is decreased by pro-inflammatory stimuli, it is now clear that this is true in vitro, but inflammatory stimuli in vivo almost universally increase TREM2 expression. Likewise, while TREM2 function is classically described as promoting an anti-inflammatory phenotype, more than half of published studies demonstrate a pro-inflammatory role for TREM2, suggesting that its role in inflammation is much more complex. Finally, these components of TREM2 biology are applied to a discussion of how TREM2 impacts NDD pathologies and the latest assessment of how these findings might be applied to immune-directed clinical biomarkers and therapeutics.

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Section: Genetics Of Trem2 In Nddsmentioning

confidence: 83%

Section: Genetics Of Trem2 In Nddsmentioning

confidence: 99%

TREM2 in Neurodegenerative Diseases

Jay

Saucken

Landreth

2017

Mol Neurodegeneration

304

283

View full text Add to dashboard Cite

show abstract

“…GWAS studies performed on individuals of East Asian origin did not detect an increase in the risk of developing AD for those carrying the TREM2 R47H variant [47–51]. These findings most likely indicate that the development of AD is multifactorial and certain populations may possess factors that compensate for the partial loss of TREM2 function.…”

Section: Trem2 Variants In Neurodegenerative Diseasesmentioning

confidence: 98%

Regulation of microglial survival and proliferation in health and diseases

Ulland

Wang

Colonna

2015

Seminars in Immunology

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Microglia play an important role in the development and maintenance of the central nervous system (CNS) under homeostatic conditions as well as during neurodegenerative diseases. Recent observations in human genomics and advances in genetic mouse models have provided insights into signaling pathways that control development, survival, proliferation and function of microglia. Alteration of these pathways contributes to the pathogenesis of CNS diseases. Here we review the current literature regarding the roles of these microglial pathways in both the normal and diseased brain and discuss areas that require further investigation.

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“…For example, the Parkinson’s disease susceptibility gene, MAPT , a major contributor to the disease in Caucasian populations, is only weakly associated with the disease in the Asian population ( 12 , 13 ). Similarly, whereas the multiple nonsynonymous variants of TREM2 are strongly associated with AD in Caucasian populations ( 3 , 4 ), these associations were not replicated in East Asian populations ( 14 – 16 ). On the other hand, an independent variant in TREM2 ( p .…”

mentioning

confidence: 95%

Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis

Zhou

Chen

Mok

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceAlzheimer’s disease (AD) is an age-related neurodegenerative disease. Genome-wide association studies predominately focusing on Caucasian populations have identified risk loci and genes associated with AD; the majority of these variants reside in noncoding regions with unclear functions. Here, we report a whole-genome sequencing study for AD in the Chinese population. Other than the APOE locus, we identified common variants in GCH1 and KCNJ15 that show suggestive associations with AD. For these two risk variants, an association with AD or advanced onset of disease can be observed in non-Asian AD cohorts. An association study of risk variants with expression data revealed their modulatory effects on immune signatures, linking the potential roles of these genes with immune-related pathways during AD pathogenesis.

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Lack of Genetic Association Between TREM2 and Alzheimer’s Disease in East Asian Population

Abstract: In our study, we found that TREM2 variant is likely not associated with AD in East Asian population.

Cited by 22 publications

References 17 publications

TREM2 in Neurodegenerative Diseases

TREM2 in Neurodegenerative Diseases

Regulation of microglial survival and proliferation in health and diseases

Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis

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