Dataset Information

Statistical power in genome-wide association studies and quantitative trait locus mapping.

ABSTRACT: Power calculation prior to a genetic experiment can help investigators choose the optimal sample size to detect a quantitative trait locus (QTL). Without the guidance of power analysis, an experiment may be underpowered or overpowered. Either way will result in wasted resource. QTL mapping and genome-wide association studies (GWAS) are often conducted using a linear mixed model (LMM) with controls of population structure and polygenic background using markers of the whole genome. Power analysis for such a mixed model is often conducted via Monte Carlo simulations. In this study, we derived a non-centrality parameter for the Wald test statistic for association, which allows analytical power analysis. We show that large samples are not necessary to detect a biologically meaningful QTL, say explaining 5% of the phenotypic variance. Several R functions are provided so that users can perform power analysis to determine the minimum sample size required to detect a given QTL with a certain statistical power or calculate the statistical power with given sample size and known values of other population parameters.

SUBMITTER: Wang M

PROVIDER: S-EPMC6781134 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Statistical power in genome-wide association studies and quantitative trait locus mapping.

Wang Meiyue M Xu Shizhong S

Heredity 20190311 3

Power calculation prior to a genetic experiment can help investigators choose the optimal sample size to detect a quantitative trait locus (QTL). Without the guidance of power analysis, an experiment may be underpowered or overpowered. Either way will result in wasted resource. QTL mapping and genome-wide association studies (GWAS) are often conducted using a linear mixed model (LMM) with controls of population structure and polygenic background using markers of the whole genome. Power analysis ...[more]

PMID: 30858595

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Project description:Genome-wide association studies (GWAS) aim to identify genetic variants related to diseases by examining the associations between phenotypes and hundreds of thousands of genotyped markers. Because many genes are potentially involved in common diseases and a large number of markers are analyzed, it is crucial to devise an effective strategy to identify truly associated variants that have individual and/or interactive effects, while controlling false positives at the desired level. Although a number of model selection methods have been proposed in the literature, including marginal search, exhaustive search, and forward search, their relative performance has only been evaluated through limited simulations due to the lack of an analytical approach to calculating the power of these methods. This article develops a novel statistical approach for power calculation, derives accurate formulas for the power of different model selection strategies, and then uses the formulas to evaluate and compare these strategies in genetic model spaces. In contrast to previous studies, our theoretical framework allows for random genotypes, correlations among test statistics, and a false-positive control based on GWAS practice. After the accuracy of our analytical results is validated through simulations, they are utilized to systematically evaluate and compare the performance of these strategies in a wide class of genetic models. For a specific genetic model, our results clearly reveal how different factors, such as effect size, allele frequency, and interaction, jointly affect the statistical power of each strategy. An example is provided for the application of our approach to empirical research. The statistical approach used in our derivations is general and can be employed to address the model selection problems in other random predictor settings. We have developed an R package markerSearchPower to implement our formulas, which can be downloaded from the Comprehensive R Archive Network (CRAN) or http://bioinformatics.med.yale.edu/group/.

Dataset Information

Statistical power in genome-wide association studies and quantitative trait locus mapping.

Publications

Statistical power in genome-wide association studies and quantitative trait locus mapping.

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