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Reproduction and In-Depth Evaluation of Genome-Wide Association Studies and Genome-Wide Meta-analyses Using Summary Statistics.

ABSTRACT: In line with open-source genetics, we report a novel linear regression technique for genome-wide association studies (GWAS), called Open GWAS algoriTHm (OATH). When individual-level data are not available, OATH can not only completely reproduce reported results from an experimental model, but also recover underreported results from other alternative models with a different combination of nuisance parameters using naïve summary statistics (NSS). OATH can also reliably evaluate all reported results in-depth (e.g., p-value variance analysis), as demonstrated for 42 Arabidopsis phenotypes under three magnesium (Mg) conditions. In addition, OATH can be used for consortium-driven genome-wide association meta-analyses (GWAMA), and can greatly improve the flexibility of GWAMA. A prototype of OATH is available in the Genetic Analysis Repository (https://github.com/gc5k/GEAR).

SUBMITTER: Niu YF

PROVIDER: S-EPMC5345724 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Reproduction and In-Depth Evaluation of Genome-Wide Association Studies and Genome-Wide Meta-analyses Using Summary Statistics.

Niu Yao-Fang YF Ye Chengyin C He Ji J Han Fang F Guo Long-Biao LB Zheng Hou-Feng HF Chen Guo-Bo GB

G3 (Bethesda, Md.) 20170310 3

In line with open-source genetics, we report a novel linear regression technique for genome-wide association studies (GWAS), called Open GWAS algoriTHm (OATH). When individual-level data are not available, OATH can not only completely reproduce reported results from an experimental model, but also recover underreported results from other alternative models with a different combination of nuisance parameters using naïve summary statistics (NSS). OATH can also reliably evaluate all reported result ...[more]

PMID: 28122950

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Project description:Linear mixed models (LMMs) are among the most commonly used tools for genetic association studies. However, the standard method for estimating variance components in LMMs-the restricted maximum likelihood estimation method (REML)-suffers from several important drawbacks: REML requires individual-level genotypes and phenotypes from all samples in the study, is computationally slow, and produces downward-biased estimates in case control studies. To remedy these drawbacks, we present an alternative framework for variance component estimation, which we refer to as MQS. MQS is based on the method of moments (MoM) and the minimal norm quadratic unbiased estimation (MINQUE) criterion, and brings two seemingly unrelated methods-the renowned Haseman-Elston (HE) regression and the recent LD score regression (LDSC)-into the same unified statistical framework. With this new framework, we provide an alternative but mathematically equivalent form of HE that allows for the use of summary statistics. We provide an exact estimation form of LDSC to yield unbiased and statistically more efficient estimates. A key feature of our method is its ability to pair marginal z-scores computed using all samples with SNP correlation information computed using a small random subset of individuals (or individuals from a proper reference panel), while capable of producing estimates that can be almost as accurate as if both quantities are computed using the full data. As a result, our method produces unbiased and statistically efficient estimates, and makes use of summary statistics, while it is computationally efficient for large data sets. Using simulations and applications to 37 phenotypes from 8 real data sets, we illustrate the benefits of our method for estimating and partitioning SNP heritability in population studies as well as for heritability estimation in family studies. Our method is implemented in the GEMMA software package, freely available at www.xzlab.org/software.html.

Dataset Information

Reproduction and In-Depth Evaluation of Genome-Wide Association Studies and Genome-Wide Meta-analyses Using Summary Statistics.

Publications

Reproduction and In-Depth Evaluation of Genome-Wide Association Studies and Genome-Wide Meta-analyses Using Summary Statistics.

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