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Statistical tests for detecting associations with groups of genetic variants: generalization, evaluation, and implementation.

ABSTRACT: With recent advances in sequencing, genotyping arrays, and imputation, GWAS now aim to identify associations with rare and uncommon genetic variants. Here, we describe and evaluate a class of statistics, generalized score statistics (GSS), that can test for an association between a group of genetic variants and a phenotype. GSS are a simple weighted sum of single-variant statistics and their cross-products. We show that the majority of statistics currently used to detect associations with rare variants are equivalent to choosing a specific set of weights within this framework. We then evaluate the power of various weighting schemes as a function of variant characteristics, such as MAF, the proportion associated with the phenotype, and the direction of effect. Ultimately, we find that two classical tests are robust and powerful, but details are provided as to when other GSS may perform favorably. The software package CRaVe is available at our website (http://dceg.cancer.gov/bb/tools/crave).

SUBMITTER: Ferguson J

PROVIDER: S-EPMC3658182 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Statistical tests for detecting associations with groups of genetic variants: generalization, evaluation, and implementation.

Ferguson John J Wheeler William W Fu Yiping Y Prokunina-Olsson Ludmila L Zhao Hongyu H Sampson Joshua J

European journal of human genetics : EJHG 20121024 6

With recent advances in sequencing, genotyping arrays, and imputation, GWAS now aim to identify associations with rare and uncommon genetic variants. Here, we describe and evaluate a class of statistics, generalized score statistics (GSS), that can test for an association between a group of genetic variants and a phenotype. GSS are a simple weighted sum of single-variant statistics and their cross-products. We show that the majority of statistics currently used to detect associations with rare v ...[more]

PMID: 23092956

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Dataset Information

Statistical tests for detecting associations with groups of genetic variants: generalization, evaluation, and implementation.

Publications

Statistical tests for detecting associations with groups of genetic variants: generalization, evaluation, and implementation.

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