Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study
ABSTRACT Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1. The Cache County Memory Study is a large, population-based sample designed for the study of memory and aging. We genotyped R47H in 2974 samples (427 cases and 2540 control subjects) from the Cache County study using a custom TaqMan assay. We observed 7 heterozygous cases and 12 heterozygous control subjects with an odds ratio of 3.5 (95% confidence interval, 1.3-8.8; p = 0.0076). The minor allele frequency and population attributable fraction for R47H were 0.0029 and 0.004, respectively. This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant.
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ABSTRACT: Background: Population stratification is a key concern for genetic association analyses. In addition, extreme homogeneity of ethnic origins of a population can make it difficult to interpret how genetic associations in that population may translate into other populations. Here we have evaluated the genetic substructure of samples from the Cache County study relative to the HapMap Reference populations and data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results: Our findings show that the Cache County study is similar in ethnic diversity to the self-reported "Whites" in the ADNI sample and less homogenous than the HapMap CEU population. Conclusions: We conclude that the Cache County study is genetically representative of the general European American population in the USA and is an appropriate population for conducting broadly applicable genetic studies.BMC Bioinformatics 05/2014; 15(Suppl 7):S8. DOI:10.1186/1471-2105-15-S7-S8 · 2.67 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
- SourceAvailable from: Surjyadipta BhattacharjeeFrontiers in Aging Neuroscience 06/2014; 6:116. DOI:10.3389/fnagi.2014.00116 · 2.84 Impact Factor
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ABSTRACT: Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.Journal of Alzheimer's disease: JAD 04/2014; DOI:10.3233/JAD-140225 · 3.61 Impact Factor