Burgess, Stephen; Thompson, Simon G; CRP CHD Genetics Collaboration; Burgess, S; Thompson, SG; Andrews, G; Samani, NJ; Hall, A; Whincup, P; Morris, R; +107 more... Lawlor, DA; Davey Smith, G; Timpson, N; Ebrahim, S; Ben-Shlomo, Y; Davey Smith, G; Timpson, N; Brown, M; Ricketts, S; Sandhu, M; Reiner, A; Psaty, B; Lange, L; Cushman, M; Hung, J; Thompson, P; Beilby, J; Warrington, N; Palmer, LJ; Nordestgaard, BG; Tybjaerg-Hansen, A; Zacho, J; Wu, C; Lowe, G; Tzoulaki, I; Kumari, M; Sandhu, M; Yamamoto, JF; Chiodini, B; Franzosi, M; Hankey, GJ; Jamrozik, K; Palmer, L; Rimm, E; Pai, J; Psaty, B; Heckbert, S; Bis, J; Anand, S; Engert, J; Collins, R; Clarke, R; Melander, O; Berglund, G; Ladenvall, P; Johansson, L; Jansson, J-H; Hallmans, G; Hingorani, A; Humphries, S; Rimm, E; Manson, J; Pai, J; Watkins, H; Clarke, R; Hopewell, J; Saleheen, D; Frossard, R; Danesh, J; Sattar, N; Robertson, M; Shepherd, J; Schaefer, E; Hofman, A; Witteman, JCM; Kardys, I; Ben-Shlomo, Y; Davey Smith, G; Timpson, N; de Faire, U; Bennet, A; Sattar, N; Ford, I; Packard, C; Kumari, M; Manson, J; Lawlor, Debbie A; Davey Smith, George; Anand, S; Collins, R; Casas, JP; Danesh, J; Davey Smith, G; Franzosi, M; Hingorani, A; Lawlor, DA; Manson, J; Nordestgaard, BG; Samani, NJ; Sandhu, M; Smeeth, L; Wensley, F; Anand, S; Bowden, J; Burgess, S; Casas, JP; Di Angelantonio, E; Engert, J; Gao, P; Shah, T; Smeeth, L; Thompson, SG; Verzilli, C; Walker, M; Whittaker, J; Hingorani, A; Danesh, J; (2010) Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables. Statistics in medicine, 29 (12). pp. 1298-1311. ISSN 0277-6715 DOI: https://doi.org/10.1002/sim.3843
Permanent Identifier
Use this Digital Object Identifier when citing or linking to this resource.
Abstract
Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.
| Item Type | Article |
|---|---|
| Faculty and Department |
Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology Academic Services & Administration > Directorate |
| Research Centre | Centre for Global Non-Communicable Diseases (NCDs) |
| PubMed ID | 20209660 |
| ISI | 278428200007 |
| Related URLs |
Downloads
Metrics & Citations
Google Scholar
