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TREM2 variants in Alzheimer's disease

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TREM2 variants in Alzheimer's disease. / Guerreiro, Rita; Wojtas, Aleksandra; Bras, Jose; Carrasquillo, Minerva; Rogaeva, Ekaterina; Majounie, Elisa; Cruchaga, Carlos; Sassi, Celeste; Kauwe, John S K; Younkin, Steven; Hazrati, Lilinaz; Collinge, John; Pocock, Jennifer; Lashley, Tammaryn; Williams, Julie; Lambert, Jean-Charles; Amouyel, Philippe; Goate, Alison; Rademakers, Rosa; Morgan, Kevin; Powell, John; St George-Hyslop, Peter; Singleton, Andrew; Hardy, John; Alzheimer Genetic Analysis Group.

In: NEW ENGL J MED, Vol. 368, No. 2, 10.01.2013, p. 117-27.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Guerreiro, R, Wojtas, A, Bras, J, Carrasquillo, M, Rogaeva, E, Majounie, E, Cruchaga, C, Sassi, C, Kauwe, JSK, Younkin, S, Hazrati, L, Collinge, J, Pocock, J, Lashley, T, Williams, J, Lambert, J-C, Amouyel, P, Goate, A, Rademakers, R, Morgan, K, Powell, J, St George-Hyslop, P, Singleton, A, Hardy, J & Alzheimer Genetic Analysis Group 2013, 'TREM2 variants in Alzheimer's disease', NEW ENGL J MED, vol. 368, no. 2, pp. 117-27. https://doi.org/10.1056/NEJMoa1211851

APA

Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., Hazrati, L., Collinge, J., Pocock, J., Lashley, T., Williams, J., Lambert, J-C., Amouyel, P., Goate, A., Rademakers, R., ... Alzheimer Genetic Analysis Group (2013). TREM2 variants in Alzheimer's disease. NEW ENGL J MED, 368(2), 117-27. https://doi.org/10.1056/NEJMoa1211851

Vancouver

Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E et al. TREM2 variants in Alzheimer's disease. NEW ENGL J MED. 2013 Jan 10;368(2):117-27. https://doi.org/10.1056/NEJMoa1211851

Bibtex

@article{163d97df175d404e96c9c056df65b6dd,
title = "TREM2 variants in Alzheimer's disease",
abstract = "BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.METHODS: We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice.RESULTS: We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P=0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P=0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease.CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.).",
keywords = "Aged, Alzheimer Disease, Animals, Brain, Exome, Genetic Variation, Genome-Wide Association Study, Genotype, Genotyping Techniques, Heterozygote, Humans, Membrane Glycoproteins, Mice, Mice, Inbred A, Mutation, RNA, Messenger, Receptors, Immunologic, Risk Factors, Sequence Analysis, DNA",
author = "Rita Guerreiro and Aleksandra Wojtas and Jose Bras and Minerva Carrasquillo and Ekaterina Rogaeva and Elisa Majounie and Carlos Cruchaga and Celeste Sassi and Kauwe, {John S K} and Steven Younkin and Lilinaz Hazrati and John Collinge and Jennifer Pocock and Tammaryn Lashley and Julie Williams and Jean-Charles Lambert and Philippe Amouyel and Alison Goate and Rosa Rademakers and Kevin Morgan and John Powell and {St George-Hyslop}, Peter and Andrew Singleton and John Hardy and {Alzheimer Genetic Analysis Group} and {Bussche van den}, Hendrik",
year = "2013",
month = jan,
day = "10",
doi = "10.1056/NEJMoa1211851",
language = "English",
volume = "368",
pages = "117--27",
journal = "NEW ENGL J MED",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "2",

}

RIS

TY - JOUR

T1 - TREM2 variants in Alzheimer's disease

AU - Guerreiro, Rita

AU - Wojtas, Aleksandra

AU - Bras, Jose

AU - Carrasquillo, Minerva

AU - Rogaeva, Ekaterina

AU - Majounie, Elisa

AU - Cruchaga, Carlos

AU - Sassi, Celeste

AU - Kauwe, John S K

AU - Younkin, Steven

AU - Hazrati, Lilinaz

AU - Collinge, John

AU - Pocock, Jennifer

AU - Lashley, Tammaryn

AU - Williams, Julie

AU - Lambert, Jean-Charles

AU - Amouyel, Philippe

AU - Goate, Alison

AU - Rademakers, Rosa

AU - Morgan, Kevin

AU - Powell, John

AU - St George-Hyslop, Peter

AU - Singleton, Andrew

AU - Hardy, John

AU - Alzheimer Genetic Analysis Group

AU - Bussche van den, Hendrik

PY - 2013/1/10

Y1 - 2013/1/10

N2 - BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.METHODS: We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice.RESULTS: We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P=0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P=0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease.CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.).

AB - BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.METHODS: We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice.RESULTS: We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P=0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P=0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease.CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.).

KW - Aged

KW - Alzheimer Disease

KW - Animals

KW - Brain

KW - Exome

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Genotype

KW - Genotyping Techniques

KW - Heterozygote

KW - Humans

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Inbred A

KW - Mutation

KW - RNA, Messenger

KW - Receptors, Immunologic

KW - Risk Factors

KW - Sequence Analysis, DNA

U2 - 10.1056/NEJMoa1211851

DO - 10.1056/NEJMoa1211851

M3 - SCORING: Journal article

C2 - 23150934

VL - 368

SP - 117

EP - 127

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 2

ER -