Dataset Information

Joint analysis of multiple phenotypes: summary of results and discussions from the Genetic Analysis Workshop 19.

ABSTRACT: For Genetic Analysis Workshop 19, 2 extensive data sets were provided, including whole genome and whole exome sequence data, gene expression data, and longitudinal blood pressure outcomes, together with nongenetic covariates. These data sets gave researchers the chance to investigate different aspects of more complex relationships within the data, and the contributions in our working group focused on statistical methods for the joint analysis of multiple phenotypes, which is part of the research field of data integration. The analysis of data from different sources poses challenges to researchers but provides the opportunity to model the real-life situation more realistically.Our 4 contributions all used the provided real data to identify genetic predictors for blood pressure. In the contributions, novel multivariate rare variant tests, copula models, structural equation models and a sparse matrix representation variable selection approach were applied. Each of these statistical models can be used to investigate specific hypothesized relationships, which are described together with their biological assumptions.The results showed that all methods are ready for application on a genome-wide scale and can be used or extended to include multiple omics data sets. The results provide potentially interesting genetic targets for future investigation and replication. Furthermore, all contributions demonstrated that the analysis of complex data sets could benefit from modeling correlated phenotypes jointly as well as by adding further bioinformatics information.

SUBMITTER: Schillert A

PROVIDER: S-EPMC4895558 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Joint analysis of multiple phenotypes: summary of results and discussions from the Genetic Analysis Workshop 19.

Schillert Arne A Konigorski Stefan S

BMC genetics 20160203

For Genetic Analysis Workshop 19, 2 extensive data sets were provided, including whole genome and whole exome sequence data, gene expression data, and longitudinal blood pressure outcomes, together with nongenetic covariates. These data sets gave researchers the chance to investigate different aspects of more complex relationships within the data, and the contributions in our working group focused on statistical methods for the joint analysis of multiple phenotypes, which is part of the research ...[more]

PMID: 26866608

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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

Joint analysis of multiple phenotypes: summary of results and discussions from the Genetic Analysis Workshop 19.

Publications

Joint analysis of multiple phenotypes: summary of results and discussions from the Genetic Analysis Workshop 19.

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