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Methods for meta-analysis of individual participant data from Mendelian randomisation studies with binary outcomes.
MedLine Citation:
PMID:  22717643     Owner:  NLM     Status:  Publisher    
Mendelian randomisation is an epidemiological method for estimating causal associations from observational data by using genetic variants as instrumental variables. Typically the genetic variants explain only a small proportion of the variation in the risk factor of interest, and so large sample sizes are required, necessitating data from multiple sources. Meta-analysis based on individual patient data requires synthesis of studies which differ in many aspects. A proposed Bayesian framework is able to estimate a causal effect from each study, and combine these using a hierarchical model. The method is illustrated for data on C-reactive protein and coronary heart disease (CHD) from the C-reactive protein CHD Genetics Collaboration (CCGC). Studies from the CCGC differ in terms of the genetic variants measured, the study design (prospective or retrospective, population-based or case-control), whether C-reactive protein was measured, the time of C-reactive protein measurement (pre- or post-disease), and whether full or tabular data were shared. We show how these data can be combined in an efficient way to give a single estimate of causal association based on the totality of the data available. Compared to a two-stage analysis, the Bayesian method is able to incorporate data on 23% additional participants and 51% more events, leading to a 23-26% gain in efficiency.
Stephen Burgess; Simon G Thompson; Crp Chd Genetics Collaboration
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-19
Journal Detail:
Title:  Statistical methods in medical research     Volume:  -     ISSN:  1477-0334     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9212457     Medline TA:  Stat Methods Med Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Public Health & Primary Care, Strangeways Research Laboratory, Cambridge, UK.
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