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Abstract
Objectives: Recently, 2 independent studies reported that a rare missense variant, rs75932628 (R47H), in exon 2 of the gene encoding the “triggering receptor expressed on myeloid cells 2” (TREM2) significantly increases the risk of Alzheimer disease (AD) with an effect size comparable to that of the APOE ε4 allele.
Methods: In this study, we attempted to replicate the association between rs75932628 and AD risk by directly genotyping rs75932628 in 2 independent Caucasian family cohorts consisting of 927 families (with 1,777 affected and 1,235 unaffected) and in 2 Caucasian case-control cohorts composed of 1,314 cases and 1,609 controls. In addition, we imputed genotypes in 3 independent Caucasian case-control cohorts containing 1,906 cases and 1,503 controls.
Results: Meta-analysis of the 2 family-based and the 5 case-control cohorts yielded a p value of 0.0029, while the overall summary estimate (using case-control data only) resulted in an odds ratio of 1.67 (95% confidence interval 0.95–2.92) for the association between the TREM2 R47H and increased AD risk.
Conclusions: While our results serve to confirm the association between R47H and risk of AD, the observed effect on risk was substantially smaller than that previously reported.
GLOSSARY
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- AgeCoDe=
- German Study on Ageing, Cognition and Dementia in Primary Care Patients;
- CI=
- confidence interval;
- FBAT=
- family-based association test;
- GSK=
- GlaxoSmithKline;
- GWAS=
- genome-wide association study;
- LOAD=
- late-onset Alzheimer disease;
- MAF=
- minor allele frequency;
- NIA=
- National Institute on Aging;
- NIA-LOAD=
- National Institute on Aging Genetics Initiative for Late Onset Alzheimer's Disease;
- NIMH=
- National Institute of Mental Health;
- OR=
- odds ratio;
- SNP=
- single nucleotide polymorphism;
- TGEN2=
- Translational Genomics Research Institute series 2;
- TREM2=
- triggering receptor expressed on myeloid cells 2
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received November 21, 2013.
- Accepted in final form July 15, 2014.
- © 2014 American Academy of Neurology
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