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Author Notes:

Corresponding Author(s): Nilüfer Ertekin-Taner Email: Taner.Nilufer@mayo.edu Carlos Cruchaga Email: cruchagc@psychiatry.wustl.edu

SCJ, MMC, CC, AMG and NET were involved with the conception, design, analysis and interpretation of data.

BAB, TK, DC, DP, SL, SK, MK, CR and TSW performed the experiments.

RM, TSW, JJL, AIL, JM, HH, TF, NRG, AMG and NET recruited and maintained the study cohorts.

CC, AMG and NET provided overall supervision of the study and acquired funding.

All authors contributed to the drafting and critical revision of the manuscript and have given final approval of the version to be published.

We are grateful to all the individuals who participated in the study and the scientists, clinicians, technicians, and administrative staff who helped in the implementation of this study.

We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis.

The authors would like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010).

MMC and NET are supported partly by GHR Foundation grants. MMC is also supported by an Alzheimer’s Association MNIRGD award.

CC was a recipient of a New Investigator Award in Alzheimer’s disease from the American Federation for Aging Research.

Author Disclosure: Dr. Graff-Radford has multicenter treatment study grants from Lilly, TauRx and consulted for Cytox.

Dr. Goate has received compensation as a member of the scientific advisory board of Cognition Therapeutics.

She has also consulted for Amgen and received compensation.

The authors declare that they have no competing interests.


Research Funding:

The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant # UL1TR000448 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.

Support for this research was provided by grants from the National Institutes of Health (P30 NS069329, R01 AG044546, and R01 AG035083); National Institute on Aging (R01 AG032990 and U01 AG046139 to NET; R01 AG09956 and P30 AG10133 to Indiana University); National Institute of Neurological Disorders and Stroke (R01 NS080820 to NET), Mayo Alzheimer’s Disease Research Center: (P50 AG0016574 to NRG-R and NET); Emory Alzheimer’s Disease Research Center (P50 AG025688); Department of Veterans Affairs (IBX001820A).

The recruitment and clinical characterization of research participants at Washington University were supported by NIH P50 AG05681, P01 AG03991, and P01 AG026276.

NIALOAD samples were collected under a cooperative agreement grant (U24 AG026395 and R01 AG041797) awarded by the National Institute on Aging.

NIALOAD samples were obtained from the National Cell Repository for Alzheimer’s Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA).

African Americans in the WHICAP sample were recruited under a research award R01AG037212.

This project was also generously supported by the Robert and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program (NRG-R).

Additional funding was provided by the Alzheimer Association (NIRG-11-200110).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • LOAD
  • African-American
  • TREM2
  • Coding variants
  • Case-control
  • P.R47H

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

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Journal Title:

Molecular Neurodegeneration


Volume 10, Number 1


, Pages 19-19

Type of Work:

Article | Final Publisher PDF


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.

Copyright information:

© Jin et al.; licensee BioMed Central. 2015

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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