Principal Investigator: Dr Philip Haycock
Department: MRC Integrative Epidemiology Unit
Institution: University of BristolTags: 15825, Mendelian randomization, web-based resource
Lead Collaborators: Dr Mattias Johansson
Collaborating Institutions and Addresses: International Agency for Research on Cancer, Genetic Epidemiology Group, 150 Cours Albert Thomas, Lyon 69008, France
1a: The aim of our research is to develop an online tool called MR-Base, www.mrbase.org, to facilitate the application of Mendelian randomization using summary data. The objectives are: 1) to collate and harmonize summary association data from a) genome-wide and b) phenome-wide association studies of all traits into a central database; and 2) to automate the Mendelian randomization analysis pipeline. MR-Base will greatly increase the accessibility of Mendelian randomization for a wide body of researchers.
1b: Mendelian randomization is an increasingly important tool for appraising causality in observational epidemiology and can be used to prioritise intervention targets for disease prevention. However, the technique requires specialist knowledge and access to very large genetic studies, which makes the approach difficult to implement for most researchers. By systematically collating and harmonizing summary association data into a single database and by automating the analysis pipeline, MR-Base will greatly increase the scope and efficiency of Mendelian randomization for identifying targets for disease prevention.
1c: We will test the association of every genetic marker against all traits (e.g. diseases and biomarkers) in UK Biobank (where sample sizes allow). The results from these analyses will be deposited into MR-Base for Mendelian randomization (a technique that uses genetic information to predict the association between exposures and disease). We will also generate correlation statistics amongst all traits in UK Biobank, to be used for comparison with results based on genetic analyses. Using the MR-Base web app, www.mrbase.org, researchers will be able to conduct Mendelian randomization analyses of their exposures and diseases of interest.
1d: We require the full cohort as well as all diseases, risk factors and biomarkers
“We are applying for an extension to our original application (#15825) that would allow us to apply JAM (joint analysis of marginal summary statistics) systematically across all GWAS summary datasets in MR-Base (www.mrbase.org), using UK Biobank as the reference panel. This will be used to support and improve MR-Base. We will also use JAM to systematically fine-map causal variants and to assess pleiotropy across all datasets in MR-Base.”
“We are applying for an extension to our original application (#15825) that would allow us to estimate the ancestral origins of UK Biobank participants using admixture methods and use the derived admixture components to match individuals on ancestry. Matching on ancestry could improve case-control study designs and so allow for improved derivation of genetic instruments and single nucleotide polymorphism (SNP) heritability estimates for use in MR-Base.”
Last updated May 17, 2017