Dataset Information

Improved polygenic prediction by Bayesian multiple regression on summary statistics.

ABSTRACT: Accurate prediction of an individual's phenotype from their DNA sequence is one of the great promises of genomics and precision medicine. We extend a powerful individual-level data Bayesian multiple regression model (BayesR) to one that utilises summary statistics from genome-wide association studies (GWAS), SBayesR. In simulation and cross-validation using 12 real traits and 1.1 million variants on 350,000 individuals from the UK Biobank, SBayesR improves prediction accuracy relative to commonly used state-of-the-art summary statistics methods at a fraction of the computational resources. Furthermore, using summary statistics for variants from the largest GWAS meta-analysis (n ? 700, 000) on height and BMI, we show that on average across traits and two independent data sets that SBayesR improves prediction R² by 5.2% relative to LDpred and by 26.5% relative to clumping and p value thresholding.

SUBMITTER: Lloyd-Jones LR

PROVIDER: S-EPMC6841727 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Improved polygenic prediction by Bayesian multiple regression on summary statistics.

Lloyd-Jones Luke R LR Zeng Jian J Sidorenko Julia J Yengo Loïc L Moser Gerhard G Kemper Kathryn E KE Wang Huanwei H Zheng Zhili Z Magi Reedik R Esko Tõnu T Metspalu Andres A Wray Naomi R NR Goddard Michael E ME Yang Jian J Visscher Peter M PM

Nature communications 20191108 1

Accurate prediction of an individual's phenotype from their DNA sequence is one of the great promises of genomics and precision medicine. We extend a powerful individual-level data Bayesian multiple regression model (BayesR) to one that utilises summary statistics from genome-wide association studies (GWAS), SBayesR. In simulation and cross-validation using 12 real traits and 1.1 million variants on 350,000 individuals from the UK Biobank, SBayesR improves prediction accuracy relative to commonl ...[more]

PMID: 31704910

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Project description:BackgroundCancer atlases often provide estimates of cancer incidence, mortality or survival across small areas of a region or country. A recent example of a cancer atlas is the Australian cancer atlas (ACA), that provides interactive maps to visualise spatially smoothed estimates of cancer incidence and survival for 20 different cancer types over 2148 small areas across Australia.MethodsThe present study proposes a multivariate Bayesian meta-analysis model, which can model multiple cancers jointly using summary measures without requiring access to the unit record data. This new approach is illustrated by modelling the publicly available spatially smoothed standardised incidence ratios for multiple cancers in the ACA divided into three groups: common, rare/less common and smoking-related. The multivariate Bayesian meta-analysis models are fitted to each group in order to explore any possible association between the cancers in three remoteness regions: major cities, regional and remote areas across Australia. The correlation between the pairs of cancers included in each multivariate model for a group was examined by computing the posterior correlation matrix for each cancer group in each region. The posterior correlation matrices in different remoteness regions were compared using Jennrich's test of equality of correlation matrices (Jennrich in J Am Stat Assoc. 1970;65(330):904-12. https://doi.org/10.1080/01621459.1970.10481133 ).ResultsSubstantive correlation was observed among some cancer types. There was evidence that the magnitude of this correlation varied according to remoteness of a region. For example, there has been significant negative correlation between prostate and lung cancer in major cities, but zero correlation found in regional and remote areas for the same pair of cancer types. High risk areas for specific combinations of cancer types were identified and visualised from the proposed model.ConclusionsPublicly available spatially smoothed disease estimates can be used to explore additional research questions by modelling multiple cancer types jointly. These proposed multivariate meta-analysis models could be useful when unit record data are unavailable because of privacy and confidentiality requirements.

Dataset Information

Improved polygenic prediction by Bayesian multiple regression on summary statistics.

Publications

Improved polygenic prediction by Bayesian multiple regression on summary statistics.

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