Association study between multiple system atrophy and TREM2 p.R47H

Kotaro Ogaki, Michael G. Heckman, Shunsuke Koga, Yuka A. Martens, Catherine Labbé, Oswaldo Lorenzo-Betancor, Ronald L. Walton, Alexandra I. Soto, Emily R. Vargas, Shinsuke Fujioka, Ryan J. Uitti, Jay A Van Gerpen, William P. Cheshire, Steven G Younkin, Zbigniew K Wszolek, Phillip Anson Low, Wolfgang Singer, Guojun D Bu, Dennis W Dickson, Owen A Ross

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective The triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not been well studied in relation to the risk of multiple system atrophy (MSA); the aim of this study was to evaluate the association between the TREM2 p.R47H variant and the risk of MSA. Methods A total of 168 patients with pathologically confirmed MSA, 89 patients with clinically diagnosed MSA, and 1,695 controls were included. TREM2 p.R47H was genotyped and assessed for association with MSA. Positive results in the Taqman genotyping assay were confirmed by Sanger sequencing. The primary comparison involved patients with pathologically confirmed MSA and controls due to the definitive MSA diagnosis in the pathologically confirmed series. Results We identified TREM2 p.R47H in 3 patients with pathologically confirmed MSA (1.79%), 1 patient with clinically diagnosed MSA (1.12%), and 7 controls (0.41%). Minimal AD pathology was observed for the pathologically confirmed MSA p.R47H carriers. For the primary comparison of patients with pathologically confirmed MSA and controls, risk of disease was significantly higher for p.R47H carriers (odds ratio [OR]: 4.39, p = 0.033). When supplementing the 168 pathologically confirmed patients with the 89 clinically diagnosed and examining the combined MSA series, the association with TREM2 p.R47H remained significant (OR: 3.81, p = 0.034). Conclusions Our preliminary results suggest that the TREM2 p.R47H substitution may be a risk factor for MSA, implying a link to neuroinflammatory processes, especially microglial activation. Validation of this finding will be important, given our relatively small sample size; meta-analytic approaches will be needed to better define the role of this variant in MSA.

Original languageEnglish (US)
Article numbere257
JournalNeurology: Genetics
Volume4
Issue number4
DOIs
StatePublished - Aug 1 2018

Fingerprint

Multiple System Atrophy
Myeloid Cells
Alzheimer Disease
Odds Ratio
Sample Size

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)

Cite this

Ogaki, K., Heckman, M. G., Koga, S., Martens, Y. A., Labbé, C., Lorenzo-Betancor, O., ... Ross, O. A. (2018). Association study between multiple system atrophy and TREM2 p.R47H. Neurology: Genetics, 4(4), [e257]. https://doi.org/10.1212/NXG.0000000000000257

Association study between multiple system atrophy and TREM2 p.R47H. / Ogaki, Kotaro; Heckman, Michael G.; Koga, Shunsuke; Martens, Yuka A.; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Walton, Ronald L.; Soto, Alexandra I.; Vargas, Emily R.; Fujioka, Shinsuke; Uitti, Ryan J.; Van Gerpen, Jay A; Cheshire, William P.; Younkin, Steven G; Wszolek, Zbigniew K; Low, Phillip Anson; Singer, Wolfgang; Bu, Guojun D; Dickson, Dennis W; Ross, Owen A.

In: Neurology: Genetics, Vol. 4, No. 4, e257, 01.08.2018.

Research output: Contribution to journalArticle

Ogaki, K, Heckman, MG, Koga, S, Martens, YA, Labbé, C, Lorenzo-Betancor, O, Walton, RL, Soto, AI, Vargas, ER, Fujioka, S, Uitti, RJ, Van Gerpen, JA, Cheshire, WP, Younkin, SG, Wszolek, ZK, Low, PA, Singer, W, Bu, GD, Dickson, DW & Ross, OA 2018, 'Association study between multiple system atrophy and TREM2 p.R47H', Neurology: Genetics, vol. 4, no. 4, e257. https://doi.org/10.1212/NXG.0000000000000257
Ogaki K, Heckman MG, Koga S, Martens YA, Labbé C, Lorenzo-Betancor O et al. Association study between multiple system atrophy and TREM2 p.R47H. Neurology: Genetics. 2018 Aug 1;4(4). e257. https://doi.org/10.1212/NXG.0000000000000257
Ogaki, Kotaro ; Heckman, Michael G. ; Koga, Shunsuke ; Martens, Yuka A. ; Labbé, Catherine ; Lorenzo-Betancor, Oswaldo ; Walton, Ronald L. ; Soto, Alexandra I. ; Vargas, Emily R. ; Fujioka, Shinsuke ; Uitti, Ryan J. ; Van Gerpen, Jay A ; Cheshire, William P. ; Younkin, Steven G ; Wszolek, Zbigniew K ; Low, Phillip Anson ; Singer, Wolfgang ; Bu, Guojun D ; Dickson, Dennis W ; Ross, Owen A. / Association study between multiple system atrophy and TREM2 p.R47H. In: Neurology: Genetics. 2018 ; Vol. 4, No. 4.
@article{e5b4f8c4125b46caadb2f37162f8f63f,
title = "Association study between multiple system atrophy and TREM2 p.R47H",
abstract = "Objective The triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not been well studied in relation to the risk of multiple system atrophy (MSA); the aim of this study was to evaluate the association between the TREM2 p.R47H variant and the risk of MSA. Methods A total of 168 patients with pathologically confirmed MSA, 89 patients with clinically diagnosed MSA, and 1,695 controls were included. TREM2 p.R47H was genotyped and assessed for association with MSA. Positive results in the Taqman genotyping assay were confirmed by Sanger sequencing. The primary comparison involved patients with pathologically confirmed MSA and controls due to the definitive MSA diagnosis in the pathologically confirmed series. Results We identified TREM2 p.R47H in 3 patients with pathologically confirmed MSA (1.79{\%}), 1 patient with clinically diagnosed MSA (1.12{\%}), and 7 controls (0.41{\%}). Minimal AD pathology was observed for the pathologically confirmed MSA p.R47H carriers. For the primary comparison of patients with pathologically confirmed MSA and controls, risk of disease was significantly higher for p.R47H carriers (odds ratio [OR]: 4.39, p = 0.033). When supplementing the 168 pathologically confirmed patients with the 89 clinically diagnosed and examining the combined MSA series, the association with TREM2 p.R47H remained significant (OR: 3.81, p = 0.034). Conclusions Our preliminary results suggest that the TREM2 p.R47H substitution may be a risk factor for MSA, implying a link to neuroinflammatory processes, especially microglial activation. Validation of this finding will be important, given our relatively small sample size; meta-analytic approaches will be needed to better define the role of this variant in MSA.",
author = "Kotaro Ogaki and Heckman, {Michael G.} and Shunsuke Koga and Martens, {Yuka A.} and Catherine Labb{\'e} and Oswaldo Lorenzo-Betancor and Walton, {Ronald L.} and Soto, {Alexandra I.} and Vargas, {Emily R.} and Shinsuke Fujioka and Uitti, {Ryan J.} and {Van Gerpen}, {Jay A} and Cheshire, {William P.} and Younkin, {Steven G} and Wszolek, {Zbigniew K} and Low, {Phillip Anson} and Wolfgang Singer and Bu, {Guojun D} and Dickson, {Dennis W} and Ross, {Owen A}",
year = "2018",
month = "8",
day = "1",
doi = "10.1212/NXG.0000000000000257",
language = "English (US)",
volume = "4",
journal = "Neurology: Genetics",
issn = "2376-7839",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Association study between multiple system atrophy and TREM2 p.R47H

AU - Ogaki, Kotaro

AU - Heckman, Michael G.

AU - Koga, Shunsuke

AU - Martens, Yuka A.

AU - Labbé, Catherine

AU - Lorenzo-Betancor, Oswaldo

AU - Walton, Ronald L.

AU - Soto, Alexandra I.

AU - Vargas, Emily R.

AU - Fujioka, Shinsuke

AU - Uitti, Ryan J.

AU - Van Gerpen, Jay A

AU - Cheshire, William P.

AU - Younkin, Steven G

AU - Wszolek, Zbigniew K

AU - Low, Phillip Anson

AU - Singer, Wolfgang

AU - Bu, Guojun D

AU - Dickson, Dennis W

AU - Ross, Owen A

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Objective The triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not been well studied in relation to the risk of multiple system atrophy (MSA); the aim of this study was to evaluate the association between the TREM2 p.R47H variant and the risk of MSA. Methods A total of 168 patients with pathologically confirmed MSA, 89 patients with clinically diagnosed MSA, and 1,695 controls were included. TREM2 p.R47H was genotyped and assessed for association with MSA. Positive results in the Taqman genotyping assay were confirmed by Sanger sequencing. The primary comparison involved patients with pathologically confirmed MSA and controls due to the definitive MSA diagnosis in the pathologically confirmed series. Results We identified TREM2 p.R47H in 3 patients with pathologically confirmed MSA (1.79%), 1 patient with clinically diagnosed MSA (1.12%), and 7 controls (0.41%). Minimal AD pathology was observed for the pathologically confirmed MSA p.R47H carriers. For the primary comparison of patients with pathologically confirmed MSA and controls, risk of disease was significantly higher for p.R47H carriers (odds ratio [OR]: 4.39, p = 0.033). When supplementing the 168 pathologically confirmed patients with the 89 clinically diagnosed and examining the combined MSA series, the association with TREM2 p.R47H remained significant (OR: 3.81, p = 0.034). Conclusions Our preliminary results suggest that the TREM2 p.R47H substitution may be a risk factor for MSA, implying a link to neuroinflammatory processes, especially microglial activation. Validation of this finding will be important, given our relatively small sample size; meta-analytic approaches will be needed to better define the role of this variant in MSA.

AB - Objective The triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not been well studied in relation to the risk of multiple system atrophy (MSA); the aim of this study was to evaluate the association between the TREM2 p.R47H variant and the risk of MSA. Methods A total of 168 patients with pathologically confirmed MSA, 89 patients with clinically diagnosed MSA, and 1,695 controls were included. TREM2 p.R47H was genotyped and assessed for association with MSA. Positive results in the Taqman genotyping assay were confirmed by Sanger sequencing. The primary comparison involved patients with pathologically confirmed MSA and controls due to the definitive MSA diagnosis in the pathologically confirmed series. Results We identified TREM2 p.R47H in 3 patients with pathologically confirmed MSA (1.79%), 1 patient with clinically diagnosed MSA (1.12%), and 7 controls (0.41%). Minimal AD pathology was observed for the pathologically confirmed MSA p.R47H carriers. For the primary comparison of patients with pathologically confirmed MSA and controls, risk of disease was significantly higher for p.R47H carriers (odds ratio [OR]: 4.39, p = 0.033). When supplementing the 168 pathologically confirmed patients with the 89 clinically diagnosed and examining the combined MSA series, the association with TREM2 p.R47H remained significant (OR: 3.81, p = 0.034). Conclusions Our preliminary results suggest that the TREM2 p.R47H substitution may be a risk factor for MSA, implying a link to neuroinflammatory processes, especially microglial activation. Validation of this finding will be important, given our relatively small sample size; meta-analytic approaches will be needed to better define the role of this variant in MSA.

UR - http://www.scopus.com/inward/record.url?scp=85060781517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060781517&partnerID=8YFLogxK

U2 - 10.1212/NXG.0000000000000257

DO - 10.1212/NXG.0000000000000257

M3 - Article

VL - 4

JO - Neurology: Genetics

JF - Neurology: Genetics

SN - 2376-7839

IS - 4

M1 - e257

ER -