Estimating Effects and Making Predictions from Genome-Wide Marker Data

Michael E. Goddard; Naomi R. Wray; Klara Verbyla; Peter M Visscher

doi:10.1214/09-sts306

Abstract

In genome-wide association studies (GWAS), hundreds of thousands of genetic markers (SNPs) are tested for association with a trait or phenotype. Reported effects tend to be larger in magnitude than the true effects of these markers, the so-called “winner’s curse.” We argue that the classical definition of unbiasedness is not useful in this context and propose to use a different definition of unbiasedness that is a property of the estimator we advocate. We suggest an integrated approach to the estimation of the SNP effects and to the prediction of trait values, treating SNP effects as random instead of fixed effects. Statistical methods traditionally used in the prediction of trait values in the genetics of livestock, which predates the availability of SNP data, can be applied to analysis of GWAS, giving better estimates of the SNP effects and predictions of phenotypic and genetic values in individuals.

Related Publications

Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry

Loïc Yengo , Julia Sidorenko , Kathryn E. Kemper +7 more

Recent genome-wide association studies (GWAS) of height and body mass index (BMI) in ∼250000 European participants have led to the discovery of ∼700 and ∼100 nearly independent ...

2018 Human Molecular Genetics 2332 citations

The NHGRI GWAS Catalog, a curated resource of SNP-trait associations

Danielle Welter , Jacqueline MacArthur , Joannella Morales +8 more

The National Human Genome Research Institute (NHGRI) Catalog of Published Genome-Wide Association Studies (GWAS) Catalog provides a publicly available manually curated collectio...

2013 Nucleic Acids Research 2876 citations

MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes

Yun Li , Cristen J. Willer , Jun Ding +2 more

Abstract Genome‐wide association studies (GWAS) can identify common alleles that contribute to complex disease susceptibility. Despite the large number of SNPs assessed in each ...

2010 Genetic Epidemiology 1877 citations

Polygenic prediction via Bayesian regression and continuous shrinkage priors

Tian Ge , Chia‐Yen Chen , Yang Ni +2 more

Polygenic risk scores (PRS) have shown promise in predicting human complex traits and diseases. Here, we present PRS-CS, a polygenic prediction method that infers posterior effe...

2019 Nature Communications 1762 citations

Power and Predictive Accuracy of Polygenic Risk Scores

Frank Dudbridge

Polygenic scores have recently been used to summarise genetic effects among an ensemble of markers that do not individually achieve significance in a large-scale association stu...

2013 PLoS Genetics 1596 citations

Publication Info

Year: 2009
Type: article
Volume: 24
Issue: 4
Citations: 127
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

Estimating Effects and Making Predictions from Genome-Wide Marker Data

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

127

OpenAlex

Cite This

APA Style

                            
                                
                                    Michael E. Goddard, 
                                
                                    Naomi R. Wray, 
                                
                                    Klara Verbyla
                                
                                et al.
                            
                            (2009). 
                            Estimating Effects and Making Predictions from Genome-Wide Marker Data. 
                            Statistical Science
                            , 24
                            (4)
                            .
                            https://doi.org/10.1214/09-sts306
                        

Identifiers

DOI: 10.1214/09-sts306