Sampling strategies for rare variant tests in case–control studies

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Optimal tests for rare variant effects in sequencing association studies.

With development of massively parallel sequencing technologies, there is a substantial need for developing powerful rare variant association tests. Common approaches include burden and non-burden tests. Burden tests assume all rare variants in the target region have effects on the phenotype in the same direction and of similar magnitude. The recently proposed sequence kernel association test (S...

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Optimal tests for rare variant effects in sequencing association studies Supplementary Material

In the case of the new family of kernels with given ρ, K = Kρ = GWRρWG. Setting μβ = Gβ and E = y − ȳ1− μβ , then Q can be rewritten as Q = (y − ȳ1)Kρ(y − ȳ1) = (E+ μβ)Kρ(E+ μβ). Note that by the spectral decomposition, Kρ = UΛU′. Since each element of E is an independent Gaussian with mean 0 and asymptotic variance 1, Q asymptotically follows ∑p j=1 λjχ 2 1(δj) with δj = μ ′ βuju ′ jμβ . Here,...

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Firth logistic regression for rare variant association tests

In association tests of sites with low minor allele frequency or count, it is known that single-variant tests are impractical to use because the results from which will be either underpowered or unreliable. Joint analyses by pooling or “collapsing” multiple variants based on annotated gene group information are thus more preferred in rare variant association tests. However, the issue remains in...

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Evaluation of pooled association tests for rare variant identification

Genome-wide association studies have successfully identified many common variants associated with complex human diseases. However, a large portion of the remaining heritability cannot be explained by these common variants. Exploring rare variants associated with diseases is now catching more attention. Several methods have been recently proposed for identification of rare variants. Among them, ...

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Comparing family-based rare variant association tests for dichotomous phenotypes

BACKGROUND It has been repeatedly stressed that family-based samples suffer less from genetic heterogeneity and that association analyses with family-based samples are expected to be powerful for detecting susceptibility loci for rare disease. Various approaches for rare-variant analysis with family-based samples have been proposed. METHODS In this report, performances of the existing methods...

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ژورنال

عنوان ژورنال: European Journal of Human Genetics

سال: 2012

ISSN: 1018-4813,1476-5438

DOI: 10.1038/ejhg.2012.58