Format

Send to

Choose Destination
Mol Neurodegener. 2015 Apr 10;10:19. doi: 10.1186/s13024-015-0016-9.

TREM2 is associated with increased risk for Alzheimer's disease in African Americans.

Author information

1
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue B8134, St. Louis, MO, 63110, USA. shengchih.jin@yale.edu.
2
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Carrasquillo.Minerva@mayo.edu.
3
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue B8134, St. Louis, MO, 63110, USA. bbenitez@DOM.wustl.edu.
4
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue B8134, St. Louis, MO, 63110, USA. skorupat@psychiatry.wustl.edu.
5
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue B8134, St. Louis, MO, 63110, USA. carrelld@psychiatry.wustl.edu.
6
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue B8134, St. Louis, MO, 63110, USA. pateld@psychiatry.wustl.edu.
7
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Lincoln.Sarah@mayo.edu.
8
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. siddukrishnan1992@gmail.com.
9
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Michaela.Kach@gmail.com.
10
Departments of Neurology, Psychiatry and Epidemiology, Columbia University, New York, NY, 10032, USA. cr2101@cumc.columbia.edu.
11
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA. cr2101@cumc.columbia.edu.
12
Departments of Neurology, Psychiatry and Epidemiology, Columbia University, New York, NY, 10032, USA. rpm2@columbia.edu.
13
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA. rpm2@columbia.edu.
14
Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30033, USA. thomas.wingo@emory.edu.
15
Division of Neurology, Atlanta Veterans Administration Medical Center, Atlanta, GA, 30033, USA. thomas.wingo@emory.edu.
16
Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30033, USA. jlah@emory.edu.
17
Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30033, USA. alevey@emory.edu.
18
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. jrmurrel@iupui.edu.
19
Indiana University Center for Aging Research, Indianapolis, IN, 46202, USA. hhendri@iupui.edu.
20
Regenstrief Institute, Inc, 410 West 10th Street, Suite 2000, Indianapolis, IN, 46202, USA. hhendri@iupui.edu.
21
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. tforoud@iupui.edu.
22
Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. graffradford.neill@mayo.edu.
23
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue B8134, St. Louis, MO, 63110, USA. alison.goate@mssm.edu.
24
Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, 660 S. Euclid Avenue B8111, St. Louis, MO, 63110, USA. alison.goate@mssm.edu.
25
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue B8111, St. Louis, MO, 63110, USA. alison.goate@mssm.edu.
26
Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 4488 Forest Park Avenue, St. Louis, MO, 63108, USA. alison.goate@mssm.edu.
27
Department of Genetics, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA. alison.goate@mssm.edu.
28
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue B8134, St. Louis, MO, 63110, USA. cruchagc@psychiatry.wustl.edu.
29
Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, 660 S. Euclid Avenue B8111, St. Louis, MO, 63110, USA. cruchagc@psychiatry.wustl.edu.
30
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Taner.Nilufer@mayo.edu.
31
Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Taner.Nilufer@mayo.edu.

Abstract

BACKGROUND:

TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer's disease (LOAD) in Caucasians of European and North-American origin. This study evaluated the role of TREM2 in LOAD risk in African-American (AA) subjects. We performed exonic sequencing and validation in two independent cohorts of >800 subjects. We selected six coding variants (p.R47H, p.R62H, p.D87N, p.E151K, p.W191X, and p.L211P) for case-control analyses in a total of 906 LOAD cases vs. 2,487 controls.

RESULTS:

We identified significant LOAD risk association with p.L211P (p=0.01, OR=1.27, 95%CI=1.05-1.54) and suggestive association with p.W191X (p=0.08, OR=1.35, 95%CI=0.97-1.87). Conditional analysis suggests that p.L211P, which is in linkage disequilibrium with p.W191X, may be the stronger variant of the two, but does not rule out independent contribution of the latter. TREM2 p.L211P resides within the cytoplasmic domain and p.W191X is a stop-gain mutation within the shorter TREM-2V transcript. The coding variants within the extracellular domain of TREM2 previously shown to confer LOAD risk in Caucasians were extremely rare in our AA cohort and did not associate with LOAD risk.

CONCLUSIONS:

Our findings suggest that TREM2 coding variants also confer LOAD risk in AA, but implicate variants within different regions of the gene than those identified for Caucasian subjects. These results underscore the importance of investigating different ethnic populations for disease risk variant discovery, which may uncover allelic heterogeneity with potentially diverse mechanisms of action.

PMID:
25886450
PMCID:
PMC4426167
DOI:
10.1186/s13024-015-0016-9
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center